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Symptom Control in
Palliative Care
5th Edition (2013)
Dr Roger Cole
For the Illawarra Shoalhaven Local Health District
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Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 01
Pain Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 02
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 02
Principles of Pain Management . . . . . . . . . . . . . . . . 02
Use of Strong Opioids . . . . . . . . . . . . . . . . . . . . . . . 02
Delirium, Agitation, Restlessness,
Twitching and Fitting . . . . . . . . . . . . . . . . . . . . . . . 24
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Severe Agitation or Restlessness in the
Terminal Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Use of Morphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03
Managing Agitation or Restlessness without
Maintaining Hypnosis until Death . . . . . . . . . . . . . . 25
Use of Oxycodone . . . . . . . . . . . . . . . . . . . . . . . . . . 03
Twitching . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Use of Fentanyl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 04
Alternative Routes for Drug Administration . . . . . 27
Use of Hydromorphone . . . . . . . . . . . . . . . . . . . . . . 05
Use of Methadone . . . . . . . . . . . . . . . . . . . . . . . . . . 05
Use of Buprenorphine . . . . . . . . . . . . . . . . . . . . . . . . 07
Circumstances Requiring Change from Oral
Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Use of Tramadol . . . . . . . . . . . . . . . . . . . . . . . . . . . . 08
Principles of Changing from Oral Drug
Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Neuropathic Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . 08
Commonly Employed Therapeutic Options . . . . . . 27
Intractable Pain and Ketamine . . . . . . . . . . . . . . . . . 09
Itching, Ulcers, Bleeding and Topical Applications . . 29
Visceral Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Itch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Epidural and Intrathecal Pain Control . . . . . . . . . . . 10
Malignant and infected ulcers . . . . . . . . . . . . . . . . . 29
Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Painful Ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Hepatic Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Haemorrhagic Areas . . . . . . . . . . . . . . . . . . . . . . . . . 30
Intravenous Drug Users . . . . . . . . . . . . . . . . . . . . . . 11
The last days of life . . . . . . . . . . . . . . . . . . . . . . . . . 31
Common Opiate Conversions . . . . . . . . . . . . . . . . . 11
Gastrointestinal Symptoms . . . . . . . . . . . . . . . . . . 13
Nausea and Vomiting . . . . . . . . . . . . . . . . . . . . . . . . 13
Important Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Constipation and Faecal Impaction . . . . . . . . . . . . . 14
Medical Palliation of Bowel Obstruction . . . . . . . . . 16
Squashed Stomach Syndrome . . . . . . . . . . . . . . . . . 17
Anorexia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Hiccups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Respiratory Symptoms . . . . . . . . . . . . . . . . . . . . . . 19
Breathlessness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Cough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Haemoptysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Death Rattle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Urinary Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . 22
Frequency and Urgency . . . . . . . . . . . . . . . . . . . . . . 22
Bladder Spasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Hesitancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Haematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Appendix: Renal Failure Doses . . . . . . . . . . . . . . . 33
Introduction
This booklet has been prepared for and on behalf of the Illawarra Shoalhaven
Local Health District to provide medical practitioners with practical therapeutic
approaches to common symptoms encountered in the palliative care setting.
It does not set out to be comprehensive, aims to be pragmatic, may be
oversimplified, and does at times reflect personal and local practices.
This booklet aims to give practitioners quick, userfriendly recipes to manage the vast majority of symptomcontrol problems we encounter in the care of terminally
ill patients. For more detailed information of drugs
prescribed for symptom management in palliative care
I recommend the web-site www.palliativedrugs.com.
Register and access the ‘formulary’ and ‘document
library’ with the option to purchase the PCF (palliative
care formulary) for personal use. There is also an
excellent Bulletin Board where a practitioner can discuss
challenging individual cases with international palliative
care colleagues.
This edition has been updated on the last publication in
2006 to include a number of new drugs: Jurnista, a longacting form of hydromorphine; Targin, which combines
Oxycontin with naloxone to combat the constipating
effect of oxycodone; Methylnaltrexone, a subcautaneous
medication for opiate-induced constipation; and Norspan
transdermal patches for pain relief. The sections on pain
management have been extensively rewritten to reflect
current approaches to the introduction of a wide range
of opiates including methadone, and the section on
neuropathic pain has been extensively reviewed with
regard to current practices.
Palliative drug administration and dosing in renal failure
has developed over the last few years and reference is
made to dose adjustments and best drug selections
for many of the prescribed medications outlined in this
edition. An appendix with a table showing renal failure
dose adjustments for commonly prescribed drugs is
included in this edition.
Symptom Control in Palliative Care - 5th Edition (2013)
The scope of this booklet is to outline guidelines
that need individual consideration at a clinical level,
with careful review and consultation with MIMS for
appropriate dose adjustments in moderate to severe
renal failure.
This booklet has been widely circulated to medical and
nursing practitioners, hospitals and aged care facilities
in our region to encourage common approaches to
symptom management. This enhances the existing high
level of interdisciplinary co-operation taking place in the
home and institutional care of people affected by various
symptoms in palliative care.
Medical practitioners are encouraged to consider the
home as the preferred setting for death if this is the
wish of patients and families. A good approach to
therapeutics and the use of available palliative care
services (including access to syringe-drivers for the
terminal phase) is a recipe to successful management of
someone dying at home.
Roger Cole FRACP
Palliative Care Specialist
Illawarra Shoalhaven Local Health District
New South Wales
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Pain Control
Introduction
Relieving pain in advanced incurable illness is essential
to alleviate the suffering experienced by both patients
and their extended family. Understanding the principles
of pain management and the application of clinical
therapeutics using appropriate drugs for different pain
situations is of vital importance in achieving consistent
success in this field. The aim, for the patient to be
continually pain free most of the time, is achievable in
around 90% of cases.
Principles of Pain Management
The following steps are recommended:
• Establish the cause of pain through a thorough history,
examination and selected investigations. Especially
consider the possibility of neuropathic pain (see page
8) which is commonly missed and may not respond well
to the usual analgesic management.
• Reduce sensory input by prescribing a peripherally
active drug (paracetamol [Panadol, Panamax] 500–
1000mg every 4 hours and/or a nonsteroidal antiinflammatory drug [NSAID]). Modified release Panadol
Osteo 665mg, 2 caps every 8 hours is recommended.
Studies have shown an equal clinical effect to
paracetamol 1G every 6 hours
• If pain persists, add the following medicines
(depending on the intensity of the pain):
• a weak opioid: codeine phosphate 30–60mg
[compounded with paracetamol in Panadeine
Forte or Codalgin Forte] orally every 4 hours;
dextropropoxyphene 32.5-65mg [compounded with
paracetamol in Digesic, Capadex or Paradex] orally
every 4 hours; tramadol [Tramal] 50-100mg orally
every four hours, or slow-release tramadol [Tramal
SR] 100-200mg orally every twelve hours.
• a strong opioid (details below): morphine [Ordine,
MS Contin, MS Mono and Kapanol]; fentanyl
[Durogesic, Denpax or Fenpatch patches and
Actiq lozenges]; oxycodone [Endone, Oxycontin,
OxyNorm and Targin]; hydromorphone [Jurnista and
Dilaudid]
The intensity of pain may be assessed by determining
which analgesics the patient has already tried,
without success. Note that 60mg codeine and 65mg
dextropropoxyphene is equivalent to roughly 5-10mg of
morphine or oxycodone.
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• Never depend on ‘as required’ prescribing alone.
The aim is to control pain and prevent it’s recurrence
through regular prescribing. Use the oral route
whenever possible.
• Consider interventions that raise the ‘pain threshold’,
including discussion of the disease, its treatment and
prognosis, counselling, relaxation techniques and
anxiolytic therapy.
• Always prescribe an aperient when starting
narcotics. For example, docusate sodium with senna
(Coloxyl with senna) – initial therapy, 1-2 tablets at
night (see page 14).
• Be prepared to prescribe treatment for nausea in half
to two-thirds of patients on narcotics. For example,
haloperidol (Serenace) 1.5–3mg immediately then
1.5–5mg at night. Consider adding metoclopramide
(Maxolon, Pramin)10-20mg every 4-8 hours if resistant
to this (see page 13). Anti-emetics may not be required
after the first week in these patients.
Use of Strong Opioids
Initiating treatment with strong opioids has changed
in recent years as a result of gaining experience in the
clinical application of newer products. These include
fentanyl patches [Durogesic, Denpax or Fenpatch
patches], buprenorphine patches (Norspan), controlledrelease oxycodone [OxyContin, Targin], modified
release hydromorphone (Jurnista), a wider dose range
and flexibility of immediate-release formulations of
oxycodone [Endone, OxyNorm capsules and liquid],
hydromorphone [Dilaudid tablets, liquid and injection],
Fentanyl Lozenges (Actiq), and a growing place for the
use of methadone [Biodone forte, Methadone syrup
and Physeptone] in opioid rotation for resistant pain
situations.
Traditionally we used to titrate liquid morphine to effect,
then continue the effective dose four-hourly with a
double dose at bed-time. This approach (of initiating
treatment with a liquid or tablet form of an immediaterelease preparation) should still be undertaken for
patients with severe or unstable pain where the opiate
requirement is difficult to predict and titration is needed.
It is a common and reasonable practice these days for
experienced practitioners to initiate treatment with a
long acting opiate (Targin or OxyContin, Durogesic or
Norspan patches, Jurnista, MS Contin, Kapanol or MS
Mono) but it is necessary to co-prescribe a number
of tablet, capsule or patch sizes to allow titration of
Symptom Control in Palliative Care - 5th Edition (2013)
the opiate. It is also important to prescribe a suitable
immediate-release preparation for ‘breakthrough pain’,
usually in one-sixth of the total daily opiate requirement
(calculated against ‘morphine equivalence’ for the
patches [see P6 on opiate conversions]). The amount of
opiate used for breakthrough pain gives an indication
about how much to increase the long acting opiate
formulation.
This range of opiates has increased flexibility and choice
with regard to appropriate prescribing. Patients who
have severe side effects, eg nausea and vomiting, on
one may tolerate another easily. A fentanyl patch is less
constipating and is preferred by patients as it doesn’t
have to be taken orally. However it doesn’t have a
readily accessible breakthrough product (Actiq lozenges
are expensive but are now on the PBS scheme for
patients who can’t tolerate morphine for breakthrough
pain) so immediate-release morphine, oxycodone or
hydromorphone are generally used for this. The fentanyl
patch is also cumbersome in unstable or progressive
pain situations. Norspan patches are useful in situations
where a low initial opiate dose is indicated (Norspan
5 ≡ morphine 2mg every 4-hours orally) and can be
supplemented by immediate release preparations as for
fentanyl. In renal failure morphine accumulates active
metabolites that complicate its use, and hydromorphone
or fentanyl (also in 50-75% the usual dose for EGFR <
20mls/min) are preferred.
Use of Morphine
Morphine is available in immediate release liquid
(Ordine) and tablet (Sevredol 10 and 20mg; Anamorph
30mg) forms; as well long-acting preparations including
sustained-release capsules (Kapanol), and controlledrelease tablets (MS Contin, MS Mono, Momex, Apotex)
and suspension (MS Contin).
Initiating Morphine
• In most patients commence a long-acting preparation
in combination with liquid morphine for breakthrough
pain. The usual starting dose (especially in patients
transferring from Digesic or Panadeine Forte) should
be 30-60mg daily given as 12-hourly MS Contin or
once daily in the case of MS Mono or Kapanol. Most
patients should also be started on Panadol Osteo
2 tablets every 8-hours. The breakthrough dose of
liquid morphine should be 1/6th of the total daily
dose for most patients (eg 10mg 4-hourly PRN for a
patient prescribed 60mg morphine a day). It will have
a clinical analgesic effect lasting 4-6 hours. Half the
breakthrough dose if it causes drowsiness. Ask the
patient to record the number of breakthrough doses
required per day over the first few days, then increase
the long-acting preparation to account for this. The
Symptom Control in Palliative Care - 5th Edition (2013)
breakthrough dose will also have to be increased
to reflect this too. Repeat this process to titrate the
morphine to effective pain relief or drowsiness. If
the patient becomes drowsy without good relief
they may have neuropathic pain (see p..) and require
specialist review if available. Once on a stable dose it is
acceptable to need occasional ‘breakthroughs’ without
further escalating the long-acting preparation.
• Opiate-naïve and elderly patients who are not severely
distressed can be started on lower doses (eg MS
Contin 5-10mg every 12 hours). In older patients it
may be better to start regular liquid morphine in a
dose of 1-2mg every 4-6 hours to establish its effect
and tolerance before introducing the long-acting
forms. This dose can be titrated up to effect then
appropriately replaced by the long-acting form. It
would be pointless, however to start such a low dose
in a patient who has been taking regular codeine,
dextropropoxyphene or tramadol without good effect.
In renal failure choose another opiate (fentanyl or
hydromorphone are recommended) as active morphine
metabolites can accumulate unpleasantly or dangerously.
If you have to use morphine then give 25% of the dose
as liquid morphine every 6-8hours (EGFR 20-50mls/min)
or introduce a smaller starting dose of 1-2mg every 6-8
hours (EGFR <20mls/min).
Use of Oxycodone
Oxycodone is available in immediate-release liquid
[OxyNorm 1mg/ml], capsules [OxyNorm 5, 10 and
20mg] and tablets [Endone 5mg], as well as long-acting,
controlled-release formulations [OxyContin 5, 10, 20, 40
and 80mg, and Targin] of various strengths. This gives it
as much flexibility as morphine for initiating strong opioid
analgesia. Like morphine, its short acting formulations
have a duration of 4-6 hours of analgesia, while its longacting formulations are given 12-hourly. The outline
above for initiating treatment with liquid or long-acting
morphine also applies to these oxycodone preparations,
bearing in mind that oxycodone is considered more
potent in a ratio 1:1.5 (eg 20mg of oxycodone is
equivalent to 30mg of morphine orally). It is safer than
morphine in renal failure and can be prescribed in normal
dose for EGFR>10mls/min.
• Targin is a recently introduced combination of longacting Oxycontin and naloxone. The naloxone is an
opiate antagonist with little oral bioavailability (<
3%) and is used for its local effect on the bowel to
reduce the side effect of constipation. Naloxone does
have a significant systemic effect in higher doses
however. While there is little data to guide dosing, it is
recommended here that Oxycontin alone is added to
Targin for doses above Targin 40/20mg twice daily.
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Use of Fentanyl
Fentanyl is a potent strong opioid available as longacting transdermal patches [Durogesic, Denpax,
Fenpatch], immediate-acting lozenges [Actiq] and as
fentanyl injections. As with the other opioids it is usually
prescribed with regular paracetamol, NSAIDs and/or
other ‘co-analgesic’ medications for optimal analgesia
(see P…). Patients generally prefer transdermal fentanyl
and it works well alongside breakthrough morphine,
oxycodone or hydromorphone. It is less constipating
than the other opioids and is excellent for continuing the
management of stable pain. It is not such a good option
for controlling unstable or progressive pain problems due
to its delayed onset of action after dose adjustments.
• The transdermal patches release fentanyl in a
controlled manner over 72 hours, with an onset
of analgesic action about twelve hours after its
application. It works by forming a sub-dermal drug
reservoir, which then drives the serum levels. This
accounts for the delayed onset of action and a
‘wash-out’ period of up to 22 hours after removing
the patch. Patches are changed every 3 days (some
patients report a wearing off of good analgesia after
two days and need to change the patch every 48
hours). Patients are advised that the first dose and any
subsequent dose increase will not be effective for 12
hours, and that they will need to rely on breakthrough
(‘as required’) doses of morphine, oxycodone or
hydromorphone in the meantime.
• Transdermal patches are available in five strengths:
Durogesic 12, 25, 50, 75 and 100, which deliver
12, 25, 50, 75 and 100 mcg per hour of fentanyl
respectively. These would be roughly equivalent to
a four-hourly, oral morphine dose of 7.5, 15, 30, 45
and 60mg respectively (equivalent oral oxycodone
would be 2/3rd of each of these morphine doses,
while equivalent hydromorphone would be 1/5th of
the morphine doses). These figures can be used to
calculate appropriate doses for breakthrough pain
(usually the 4-hour equivalent dose, eg 30mg morphine
and for transferring patients between patches and the
different opioids.
• Being aware of the morphine equivalence of each
patch size, gives the prescriber a sense of patch
potency and also predict the correct breakthrough
dose of morphine and other opiates. For each increase
of 25mcg/hr the roughly equivalent oral morphine
dose increases in 15mg Q 4-hourly steps. Thus a
25mcg/hr patch is equivalent to 15mg oral morphine
every 4 hours, a 50mcg/hr patch is equivalent to
30mg every 4-hours, and so on. The equivalent
4-hourly dose is also the oral breakthrough dose. For
oxycodone this dose would be 10mg orally every four
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hours (2/3rd morphine dose) for each 25mcg/hr patch,
while hydromorphone would be 3mg orally every
4-hours (1/5th morphine dose). If these breakthrough
medications are given parenterally (usually SC) then
half the oral dose applies.
• When commencing patients on fentanyl patches, be
aware of the opiates that have been inadequate for
good pain control. Most still symptomatic patients
transferring from regular tramadol (400mg daily)
Panadeine Forte (8-10 daily), Digesic (8-10 daily) or
oxycodone (30-60 mg daily) will need a 25 mcg/hr
patch with liberal PRN breakthrough medication over
the first 24-48 hrs. These patients are likely to need
a 50 mcg/hr (or higher) maintenance dose. Careful
telephone review and prescribing more than one patch
strength plus the breakthrough medications will enable
the practitioner to titrate the dose effectively.
• For opioid-naive patients or those without major
distress on lower doses of the above medications, the
starting dose should be 12 mcg/hr and breakthrough
requirements over the first 24-48 hrs will guide
maintenance prescribing. Practitioners should be
aware that this fentanyl dose is still equivalent to
45mg oral morphine a day, which might be too much
for opioid naïve patients, especially the elderly. An
alternative approach would be wiser in some of these
patients (eg Norspan-5 which is equivalent to 12 mg
oral morphine daily).
• For patients with progressive pain on fentanyl patches,
the situation can often be managed by using regular
breakthrough medication while increasing the patches.
An alternative is to continue the current dose of
fentanyl and titrate regular liquid or subcutaneous
morphine (or the equivalent oxycodone or
hydromorphone) until analgesia is achieved, and then
adjust to the appropriate patch dose.
• Fentanyl lozenges [Actiq] are now available on the
PBS (for palliative cancer patients who don’t tolerate
morphine as a breakthrough medication) in 200,
400, 600 and 800, 1200 and 1600mcg strengths
for breakthrough pain. They are sucked and moved
around the oral cavity using the applicator (hence the
term ‘fentanyl lollypop’) to maximize mucosal contact.
Fentanyl is rapidly absorbed during this process
and the lozenge is removed from the mouth when
pain is controlled or excessive opioid effects appear
(drowsiness). The right strength of fentanyl lozenge is
not easy to predict with wide individual variability but
it generally recommended to start on the 400 mcg size
with most patients.
• Fentanyl injections come in a concentration of
100mcg/2ml or 500mcg/10ml. The other fentanyl
preparation are equivalent to parenteral administration
Symptom Control in Palliative Care - 5th Edition (2013)
(transdermal and transmucosal absorption) so
subcutaneous fentanyl infusions can replace the
patches at exactly the same rate per 24 hours. If used
for breakthrough pain a dose equivalent of 2-4 hours
of the fentanyl delivered by the patch is recommended
(eg 50-100mcg subcutaneously, 2-4-hourly PRN in a
patient on Durogesic 25). This is not very practical in
patients on higher strength patches as the volume for
injection becomes too high.
Use of Hydromorphone
Hydromorphone is a synthetic derivative of morphine
and is available in a long-acting modified-release tablet
(Jurnista 4, 8, 16, 32 and 64mg), as instant-release tablets
[Dilaudid 2, 4, and 8mg], as an oral liquid [Dilaudid oral
liquid 1mg/ml] and in an injectable form (with 2mg/ml,
10mg/ml and 50mg/5ml concentrations). Its efficacy
and side-effects are similar to morphine, although it
has a higher potency (1mg hydromorphone ≡ 5mg of
morphine). Hydromorphone has less active metabolites
than morphine and is a better choice of analgesic in
patients with renal failure (EGFR < 50ml/min).
• Hydromorphone may be introduced as the convenient
once daily modified-release tablet Jurnista in a dose
of 4-8 mg in still symptomatic patients transferring
from regular tramadol (400mg daily) Panadeine
Forte (8-10 daily), Digesic (8-10 daily), oxycodone
(10- 20 mg daily) or morphine (15-30mg daily). Use
additional breakthrough doses of an immediate release
preparation in 1/6th of the Jurnista dose given orally
every four-hours PRN. The Jurnista dose can then be
titrated according to the breakthrough requirements,
noting however that Jurnista accumulates to a ‘steady
state’ by its fourth dose.
• In opioid-naïve and elderly patients, the starting
dose of 4mg may be too high (unless there is severely
distressing pain). In such cases it would be wise to
initiate a low dose of Dilaudid oral liquid (0.25–0.5mg
every four hours) and titrate to response before
considering substituting Jurnista. It might be a better
alternative to use another opiate such as MS Contin or
Oxycontin in such cases, as these are available in lower
initial dose-equivalence.
• To convert oral to the equivalent subcutaneous dose of
hydromorphone give half the oral dose.
Use of Methadone
Methadone is a synthetic strong opioid with some
unique characteristics, available on the PBS as 10mg
tablets (Physeptone), a 5mg/ml solution (methadone
syrup) or as a 10mg/ml injection (Physeptone). As
well as being an opioid-receptor agonist, it inhibits
Symptom Control in Palliative Care - 5th Edition (2013)
serotonin reuptake and is an NMDA-receptor-channel
blocker. These properties probably contribute to often
impressive benefits in opiate-resistant pain, especially
in neuropathic pain (see page 8). Patients are generally
transferred from another opiate (eg morphine) when it
has been determined that this is not working despite
optimal or high doses, combined with appropriate
‘co-analgesics’ such as amitriptyline, an anticonvulsant
and dexamethasone. Unfortunately it has very complex
pharmacokinetics with a long and unpredictable half-life
(8-75 hours) so the drug accumulates on repeated doses.
As ‘steady-state’ may be reached over a week or more
on the same dose, patients initially relieved of pain may
later develop coma and respiratory depression. For these
reasons methadone should only be prescribed under the
supervision of someone experienced in its application
and requires daily telephone-monitoring at least while
stabilizing the patient’s dose over the first week. The
dosing approach recommended by MIMS is potentially
dangerous and not recommended here.
Important note: Methadone can prolong the QT interval
on ECG and its introduction has been associated (very
rarely and usually in higher doses than we generally
use in palliative care) with sudden death due to
complex ventricular tachycardia (torsades de pointes).
Caution is advised in patients at risk of prolonged QT
interval including cardiac hypertrophy, hypokalaemia,
hypomagnesaemia, diuretic use with electrolyte
abnormalities, calcium channel blockers, tricyclic
antidepressants, neuroleptic drugs and a history of
arrhythmias (see MIMS for more detailed list). If there is
concern an ECG should be obtained before considering
methadone.
The following international guidelines are accepted
ways of initiating treatment with, and transferring over
to methadone from morphine. It is acknowledged here
that these approaches to transferring from high doses
of other opiates are complex and often confusing, even
in a palliative care unit with developed guidelines. As
a consequence of this I have included a section of a
personal and regional approach (Method 3 below) that
can be managed effectively in a community setting for
most patients.
For opiates other than morphine, first convert to their
morphine-equivalence and proceed from there (see page
11).
Initiating Treatment with Methadone
When prescribing oral methadone as a first-choice strong
opioid: start on methadone 5mg q12-hourly and 5mg
q3-hourly PRN. (use half these doses in the elderly). If
pain relief remains minimal, consider increasing to 10mg
q12-hourly after 1–2 days (and 5mg q3-hourly PRN), but
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generally do not increase the regular dose for one week.
If necessary, continue to titrate the regular dose upwards
by about 1/4–1/3 once a week, guided by PRN use with
higher regular doses, increase the PRN dose to 1/4 of the
q12-hourly dose.
Transferring from Morphine
There is no single potency ratio for methadone and other
opioids. When switching from morphine, the eventual
24h dose of methadone is typically 5–10 times smaller
than the previous dose of morphine, sometimes 20–30
times smaller, and occasionally even smaller. Inevitable
accumulation is the reason for the week-long intervals
between adjustments in the regular dose. Switching
to methadone must be closely supervised, often as
an inpatient. The following two methods are the most
frequently referenced amongst palliative care services.
The third method is a simplified version that we have
developed regionally that is more practical particularly
for community patients.
Method 1
(Morley and Makin, 1998 [slightly modified])
1.Stop regular short-acting morphine abruptly when
starting the methadone. If switching from a slowrelease morphine formulation give the first dose of
methadone 6 hours after the last dose of the 12-hourly
preparation, or 12 hours after the last dose of a 24hour preparation.
2.Give a single loading dose of oral methadone equal
to 1/10th of the previous total 24-hour oral morphine
dose, up to a maximum of 30mg. If very elderly or
cachectic, omit the loading dose.
3.Give 1/3rd of the loading dose of methadone q3hourly PRN, up to a maximum of 10mg per dose.
4.For patients in severe pain and who are unable to
wait 3 hours before giving the next methadone dose,
prescribe 50-100% of the breakthrough dose of
morphine (or other opioid) that was used before the
switch on a 2-4 hourly PRN basis.
5.On Day 6, the amount of methadone taken over the
previous 2 days is noted and divided by 4 to give a
regular q12-hourly dose, and 1/4 of this regular q12hourly dose is given q3-hourly PRN.
6.If 2 or more doses/day of PRN methadone continue to
be needed, the dose of regular methadone should be
increased once a week, guided by PRN use.
7.If the patient becomes persistently drowsy, that
drowsiness is unlikely to wear off in less than 24-hours.
Stop methadone for 24 hours and recommence in
half to two-thirds the dose and continue to titrate
according to pain response and drowsiness. Continue
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PRN breakthroughs of alternative opiate during this
time unless patient is too drowsy.
Method 2
(Blackburn et al, 2002 [slightly modified])
1.Stop regular short-acting morphine (or other opiate)
abruptly when starting the methadone. If switching
from a slow-release morphine formulation give the first
dose of methadone 6 hours after the last dose of the
12-hourly preparation, or 12 hours after the last dose of
a 24-hour preparation. This should be timed with the
loading dose below.
2.Give a loading dose of 1/10th of the previous total 24hour oral morphine dose, up to a maximum of 30mg
of methadone at bedtime. If very elderly or cachectic,
omit the loading dose.
3.Prescribe 1/2 of the loading dose as a regular q12houly dose (starting on the same day at bedtime), and
give 1/4 of the regular q12-hourly dose q3-hourly PRN.
4.In the event of severe uncontrolled pain, despite
repeated PRN doses, a second loading dose can be
given. This is most likely in the first 48 hours after the
switch.
5.If the patient is very drowsy, omit one dose and then
continue with a reduced regular dose.
6.On Day 6, the amount of methadone taken over the
previous 2 days is noted and divided by 4 to give a
regular q12-hourly dose, and 1/4 of this regular q12hourly dose is given q3-hourly PRN.
7.If 2 or more doses/day of PRN methadone continue to
be needed, the dose of regular methadone should be
increased by about 1/4–1/3 once a week, guided by
PRN use.
8.If the patient becomes persistently drowsy that
drowsiness is unlikely to wear off in less than 24-hours.
Stop methadone for 24 hours and recommence in
half to two-thirds the dose and continue to titrate
according to pain response and drowsiness. Continue
PRN breakthroughs of alternative opiate during this
time unless patient is too drowsy.
Method 3
(personal approach)
1.Stop regular short-acting morphine abruptly (or other
opiate) when starting the methadone. If switching
from a slow-release morphine formulation give the first
dose of methadone 6 hours after the last dose of the
12-hourly preparation, or 12 hours after the last dose of
a 24-hour preparation. This should be timed with the
loading dose below.
2.Give a loading dose of 1/10th of the previous total 24hour oral morphine dose, up to a maximum of 30mg
Symptom Control in Palliative Care - 5th Edition (2013)
of methadone at bedtime. If very elderly or cachectic,
omit the loading dose.
3.Give 1/3rd of the loading dose q6-hourly regularly.
4.Use the previous breakthrough medication every 2-4
hours PRN in full dose (ie morphine, oxycodone, etc).
5.Make a daily phone call initially to assess progress.
6.Continue current management if the patient is still in
pain without excessive drowsiness over the first 24-48
hours. Using the same dose, reduce dose interval to
q8-hourly after 24-48 hours in patients who become
pain-free, and be prepared to reduce further by
halving this dose and giving it q6-hourly regularly over
the next 24-48 hours. This progressive dose reduction
and use of the previous opiate for breakthrough pain
anticipates methadone accumulation and attempts to
avoid excessive drowsiness. In patients who become
pain free in the first 24-48 hours the maintenance
dose is often a quarter to one-half of the initial
dose (progressively titrated in 24-48 hour intervals
by dropping to same dose q8-hourly followed by
half this dose q6-hourly) and I aim for the same but
titrate upwards again if pain begins to return without
drowsiness. The correct dose can usually be achieved
by daily or 2nd-daily review in one week in most
uncomplicated cases.
7.If the patient is still in pain without drowsiness after
48 hours increase the dose by approximately 50%
(possibly by 100% if severely distressed, although such
patients should probably be admitted at this point)
and continue the alternative opiate for breakthrough
pain. If they become pain free over the next 24-48
hours then this probably represents the maintenance
dose but it should be reduced if the patient becomes
too drowsy.
8.After establishing the total daily dose give half of
this every 12 hours. Use ¼ of the 12-hourly dose
for breakthrough pain q3-hourly PRN. Increase the
12-hourly dose of methadone by ¼ to 1/3rd once a
week if 2 or more breakthrough doses continue to be
required.
9.If the patient becomes persistently drowsy that
drowsiness is unlikely to wear off in less than 24-hours.
Stop methadone for 24 hours and recommence in
half to two-thirds the dose and continue to titrate
according to pain response and drowsiness. Continue
PRN breakthroughs of alternative opiate during this
time unless patient is too drowsy.
Use of Buprenorphine
Despite being an opioid agonist-antagonist analgesic
buprenorphine has not been shown to have a ‘ceiling’
to its analgesic effect in clinical trials (ie the dose can be
Symptom Control in Palliative Care - 5th Edition (2013)
increased exponentially until benefit or side-effects limit
its use). In Australia it is available in three transdermal
(TD) patch sizes, Norspan 5, 10 and 20, releasing 5, 10
and 20mcg/hr of buprenorphine. These are changed
once-weekly. It is also available as sublingual tablets
(Temgesic 0.2mg; Subutex 0.4mg, 2mg and 8mg;
Suboxone preparations combined with naloxone for drug
dependency programmes) and as an injection (Temgesic
300mcg/ml). None of these are PBS-listed for pain
management although Temgesic sublingual tablets come
in packs of 50.
• Buprenorphine TD patches are much more frequently
prescribed overseas in the management of chronic,
severe cancer pain. This has been facilitated by the
availability of 35-70mcg/hr patches that are changed
every 4-days. Experience suggests that doses well
in excess of the manufacturers recommended upper
limit of 140mcg/hr can be applied with breakthrough
doses of morphine or morphine equivalent opiates
being completely effective despite the theoretical
opiate antagonistic action of buprenorphine (this does
not affect the µ-receptor however). Bupernorphine is
considered potentially better in neuropathic pain, to
cause less hyperalgesia and to be less constipating
than morphine.
• The oral morphine equivalent for Norspan patches is
2mg every 4 hours for each 5mcg/hr of Norspan (ie
Norspan 5 ≡ 2mg q4-hourly; Norspan 10 ≡ 4mg q4hourly and so on). Another way of determining the
oral morphine equivalent is to multiply the patch dose
in mcg/hr by a factor of 2.4 to get the total daily oral
dose of morphine in mgs (eg Norspan 10 ≡ 24mg oral
morphine daily).
• Sublingual tablets are probably not the ideal
breakthrough medications for patients on Norspan
patches. They have a 50% bioavailabilty and are only
slowly systemically absorbed after an initial rapid
mucosal absorption. It can take an hour or more for
analgesic effect and the effect can then last for 6-7hrs
(compared to ~ 4 hrs for morphine) which is too long.
They are also approximately 80 times as potent as
morphine so 0.2mg ≡ 16mg oral morphine which is
unsuitable until the Norspan dose is 40mcg/hr. The
recommendation here is to prescribe oral morphine,
oxycodone or hydromorphone in roughly equivalent q
4-hourly doses as the breakthrough medication (eg for
Norspan 10 use morphine 4mg, oxycodone 2.5mg or
hydromorphone 1mg q4-hourly PRN).
• TD Norspan patches will initially require 24 hours to
take effect and up to 3 days to reach maximal effect.
This is true of initiating treatment and changing
the dose. This makes Norspan unsuitable for the
management of pain where rapid dose escalation is
required. It is however an excellent option for initiating
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low-dose opiates including the elderly in residential
settings where there are limited registered nurses
available for drug administration, such as nursing
homes.
• When a Norspan patch is removed its effect reduces
by approximately 50% in the first 24hrs and it then
takes 2-3 days to wear off completely.
• Inflammation and urticaria at the patch site are
relatively common. This can be prevented in some
cases by waving the patch in the air before application
to enable alcohol to evaporate. Avoid re-using
inflamed sites and cease altogether if the reactions are
severe or upsetting to the patient.
• Buprenorphine is a relatively safe opiate analgesic in
renal failure. The parent drug doesn’t accumulate and
isn’t removed by dialysis, while its principal metabolite
norbuprenorphine has no central action of clinical
significance.
Use of Tramadol
Tramadol [Tramal] has a dual action, acting as an opioid,
and by presynaptic, serotonin reuptake blockade (cf
tricyclic antidepressants). These analgesic actions are
synergistic, without antidepressant or anticholinergic
effects. Its potency is roughly equivalent to codeine,
with lower adverse opioid effects including constipation.
As it lowers the seizure threshold it should be used with
caution in epileptics, and can interact with other drugs,
including antidepressants and psychotics, that also have
this effect. Tramadol is available in short-acting (Tramol
50mg capsules), sustained-release (Tramal SR 100, 150
and 200mg tablets; Durotram XR Once-daily SR 100, 200
and 300mg tablets), oral drop (100mg/ml) and injectable
(100mg/2ml) forms.
• Dose: 50-100mg capsules orally four times a day or
Tramal SR 100-200mg every twelve hours, or Durotram
XR 100-400mg once daily. Breakthrough doses of the
50mg capsules can be given to supplement Tramal
SR or Durotram XR up to a maximum of 400mg of
tramadol per day. Alternatively give morphine or
alternative strong opiate for breakthrough pain using
the equation tramadol 100mg ≡ 10 mg morphine to
estimate a reasonable breakthrough dose.
• Changing to morphine: Commence morphine 10mg
orally every four hours in patients needing stronger
analgesia (from tramadol 400mg orally a day), then
titrate the morphine to effect as described above in
the section on morphine (P…).
• Serotonin toxicity (serotonin syndrome) has been
occasionally reported in patients receiving another
serotoninergic drug (eg SSRI antidepressants).
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Neuropathic Pain
Neuropathic pain may not respond fully to the general
analgesic approaches described above. It is due to
compression or infiltration of nerves by tumour, or to
painful peripheral neuropathy. It may be associated
with clinical evidence of deafferentation (abnormal or
absent sensation in the painful area). The following
approaches are recommended in addition to the
use of opiates and peripherally active analgesics.
Steroids are recommended for a rapid response, while
the addition of either amitriptyline, gabapentin or
pregabalin has been shown to be equally effective
in clinical trials. Furthermore the prescribing of
amitriptyline with gabapentin or pregabalin has been
shown to be better than one drug alone in difficult
cases. Using two anticonvulsants together has not
been shown to have extra benefit. It may be better to
favour amitriptyline where there is numbness, burning
or painful paraesthesia, although the evidence-base for
this is limited. Consultation with a palliative care or pain
specialist is also recommended.
For nerve root compression/infiltration:
• Dexamethasone (Dexmethsone): Give 8mg
immediately then 8mg in the morning daily for 72
hours, reducing to 4mg each morning for 48 hours. If
pain control remains good, maintain with 2–4mg each
morning in patients who are in the terminal phase.
Otherwise attempt to withdraw completely over three
weeks while introducing an anticonvulsant and/or
amitripyline etc (see below) for long-term management
• Anticonvulsants: If there is nil or only a partial response
to dexamethasone in terminal phase patients, add one
of the following anticonvulsants or an antidepressant
(see below).
• Pregabalin (Lyrica) is now PBS-listed and so the drug
of choice for most patients. Start with 75mg every
12 hours, and increase to 150mg every 12 hours
after 3 days if necessary (initiate treatment in a lower
dose of 25-50mg every 12 hours for the frail and
elderly). If the symptoms persist after another 7 days,
increase to 300mg every 12 hours. See appendix for
dosing patients with renal failure.
• Gabapentin (Neurontin) is the best option where
pregabalin is either toxic or ineffective. However
it is not listed on the PBS scheme in Australia for
neuropathic pain (it is on the RPBS [repatriation]
scheme), and can be used in patients with
mesothelioma covered by the dust-diseases board.
With gabapentin, start on 100mg every 8 hours
increasing by 100mg every 8 hours daily, up to
300mg every 8hours unless pain is controlled on
a lower dose (introduce more gradually in the frail
Symptom Control in Palliative Care - 5th Edition (2013)
and elderly). Then increase the dose weekly from
300-600-900-1200mg every 8 hours or until there is
a response. See appendix for dosing patients with
renal failure.
• Sodium valproate (Epilim) is accessible and easy to
prescribe, starting with 500mg at night, increasing
to 1G if no benefit after 3 days (start with 200mg in
the elderly, quickly increasing to twice daily if well
tolerated).
• Carbamazepine (Tegretol) 100-400mg every 12
hours (but high frequency of side effects) may also
be considered.
• Antidepressants: Amitripyline (Endep) is a reasonable
first choice with plenty of evidence based research to
support its use here. However nortriptyline (Allegron)
and imipramine (Tofranil, Toleride) are also considered
effective if it is not well tolerated. Of the other classes
of antidepressants the SNRI drugs venlafaxine (EfexorXR) and duloxetine (Cymbalta) have the most evidence
to support their use at this time, although a number
of SSRI drugs may be effective. Of these sertraline
(Zoloft) or citalopram (Cipramil) are recommended for
their lower incidence of side-effects.
• Amitriptyline: commence 10mg nocte, increasing
by 10mg daily to 2nd-daily up to a maximum dose
of 50mg nocte (the max dose of amitriptyline is
150mg nocte but there is little evidence for benefit
on neuropathic pain above 50mg nocte). Add an
anticonvulsant if there is residual pain a week after
reaching 50mg nocte.
• Nortiptyline: as for amitriptyline above.
• Imipramine: as for amitriptyline above
• Venlafaxine: commence 37.5mg nocte, increasing
to 75mg nocte in 1 week if necessary. A further
increase to 150mg nocte could be considered for
residual pain 2 weeks later in patients with normal
renal function.
• Duloxetine: commence 30mg daily increasing to
60mg daily in patinets without severe renal failure
(EGFR < 30mls/min). Further increase to a maximum
of 120mg/day can be considered if symptoms
persist.
• Local Anaesthetic Cogener: Most palliative
care physicians would occasionally consider the
introduction of a local anaesthetic cogener (lignocaine
infusion, flecainide [Tambocor, Flecatab]) when severe
residual neuropathic symptoms persist despite the
above measures, as well as the failure to control
symptoms with ketamine (see next section) and opiate
rotation to methadone. It is noted here that the place
of ketamine is now controversial. In the most severe
cases a subcutaneous infusion of lignocaine can be
Symptom Control in Palliative Care - 5th Edition (2013)
trialed with maintenance on oral flecainide. Otherwise
commence oral flecainide alone. Each patient should
be considered on an individual basis and practitioners
are requested to consult with MIMS with regard to risk
factors. It may be advisable to obtain an ECG prior to
this intervention.
• Lignocaine infusion (regional approach): Give 100mg
SC statim (5mls 2% lignocaine), followed by 600mg
by continual SC infusion over 24hrs. Increase the
dose to 1200mg if necessary after this time. If pain
is well-controlled, commence flecainide 50-100mg
twice daily, increasing to 150mg twice daily after 4
days if symptoms return. If pain not well-controlled,
abandon the trial of local anaesthetic cogener.
• Flecainide: Commence 50mg twice daily, increasing
by 50mg twice daily up to a maximum of 150mg
twice daily.
• Other options include opiate rotation to methadone,
ketamine infusion (see p…) and clonidine (Catapress)
25-100 mcg every 8-hours.
Important Note: Narcotic analgesic drugs are usually
prescribed up to the point of drowsiness to establish
the degree of effectiveness in these situations. Further
increases are a recipe for restlessness, agitation or
oversedation of the patient. Some patients resist all these
therapeutic interventions and may be considered for
interventional approaches, including nerve blocks, and
epidural or intrathecal analgesic approaches. Patients
who are in the end-stages might be better managed
with sedation if symptoms are severe. Many patients
are able to accept the limitations of treatment and use
frequent (eg half-hourly) doses of breakthrough opioid
medications for particularly painful exacerbations.
Intractable Pain and Ketamine
Ketamine, an anaesthetic induction agent, had an
established role in control of intractable pain including
reported efficacy with neuropathic pain, incident pain (ie
caused by movement) and cytotoxic-induced mucositis.
However an Australian study has shown it to be not
superior to placebo across this range of complex pain.
This has led to controversy about its use but ‘the jury’
is out on certain aspects of study-design, and many
practitioners continue to use burst or oral ketamine
as a trial in difficult cases. A personal preference is to
introduce oral ketamine, limiting side effects and making
it relatively easy to withdraw if there is toxicity.
Ketamine has a propensity to cause tachycardia, a
sense of disassociation and hallucinations. The latter
may be dose-limiting, though co-prescribing diazepam,
midazolam or haloperidol can settle hallucinations or
‘strange feelings’. In our unit we usually mix midazolam
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5mg with the ketamine dose, given as a subcutaneous
infusion over 24 hours.
A common approach is referred to as ‘burst ketamine’ in
which a short burst of ketamine is given over a number
of days then stopped. This is thought to reset pain
transmission and inhibitory pathways in the central
nervous system such that pain may respond dramatically
and then continue to be controlled on the previously
ineffective analgesic regimen. Care must be taken as
opiate toxicity can result due to a rapid reduction in
analgesic requirements (see below).
• Burst Ketamine: Begin with 1-2.5mg/kg/24 hours by
continual subcutaneous infusion, and titrate to effect.
In practical terms start with 100mg/24 hours on day
1. If effective, continue this dose for three days then
cease. If not, then increase to 300mg/24 hours on day
2. If this dose is effective continue for three days, then
cease. If not, then increase to 500mg/24 hours on day
3 and continue for 3 days if effective. This upper limit
of 500mg/24 hours is arbitrary and higher doses are
safe if the patient tolerates the treatment (3.6G/24
hours have been reported). I would go higher than
500mg in the same 200mg steps if a partial response
was observed at 500mg, although I have never used
more than 700mg/24 hours.
• Responses: In the best-case scenario the pain remains
controlled after stopping the infusion. It may return
again after an interval of weeks or months and can
then respond to another ‘burst’. If pain returns after
stopping the infusion then the patient will need to
be maintained on continual subcutaneous or oral
ketamine (see below).
• Oral ketamine: When used for maintenance, oral
ketamine is given (from the ampoules) in 1/3rd of the
total daily dose that was effective by subcutaneous
infusion. This allows for ‘first pass’ enhancement of
its effect through active metabolites. It doesn’t taste
too good but can be flavoured in cordial (50mg/5ml).
The oral dose needs to be divided into four or more
administrations daily as it can give a ‘hit’ effect with
unpleasant side effects compared to the steady state
levels of a continual infusion. If treatment is to be
initiated orally start with 10mg q6-hourly. Increase the
dose in 10mg steps up to a maximum of 50mg q6houlry (again this is arbitrary and doses up to 200mg
q6-hourly have been reported). Continue the effective
dose for three days then cease, and follow the steps
given for infusions above thereafter.
• Concurrent Treatment: Ketamine, if effective, may
lead to a substantial reduction in the concurrent
opiate dose through improved analgesia. Bear in mind
that your patient may become excessively drowsy
or develop hallucinations due to opiate toxicity.
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This is relatively easy to manage by dose reduction
of short-acting morphine but it could be more of a
problem with slow-release preparations, methadone or
transdermal fentanyl. It is wise to recommend transfer
to a short-acting product before starting the infusion.
• Severe Pain: in a patient with severe pain it may be
necessary to use morphine and midazolam in doses
that semi-sedate, whilst introducing ketamine. This
might require parenteral hydration until such treatment
can be reduced.
• Site reactions: Some patients develop inflammatory
reactions, including sterile abscesses at the infusion
sites. These can be stopped by adding 0.5-1mg of
dexamethasone to the infusion.
• Drug compatibility: Ketamine is compatible with
morphine sulphate, metoclopramide, haloperidol,
midazolam and low-dose dexamethasone in the
syringe-driver.
Visceral Pain
Like neuropathic pain, visceral pain is relatively insensitive
to narcotics. The following treatments are recommended:
• Hepatic pain which is secondary to capsular distension:
dexamethasone 4mg daily in addition to other
analgesic measures
• Genito-urinary pain (dysuria, bladder spasms, renal
colic): See page 22.
• Gastrointestinal colic: See page 16.
Epidural and Intrathecal Pain
Control
Patients with intractable pain (especially neuropathic)
may only respond to epidural or intrathecal infusions
of opiates, local anaesthetics, clonidine or ketamine.
While it is not within the scope of this book to detail
such approaches it is useful to know the basic recipes
for success and safety, though consultation with a pain
consultant (usually an anaesthetist) experienced in these
techniques is essential. I have outlined basic recipes for
lumbar epidural and intrathecal infusions of morphine
plus bupivacaine below, suitable for pain beneath the
umbilicus. For thoracic and cervical infusions the doses
are more conservative.
• Typical Epidural Recipe (Morphine plus Bupivacaine):
• Morphine – Begin with 1/30th of the daily oral
morphine dose (or 1/15th parenteral dose) up to a
maximum initial infusion of 10mg per 24 hours. For
opioid naive patients begin with 1-3mg per 24 hours.
With severe pain the dose of morphine may need to
be progressively increased up to 50mg or more per
24 hours.
Symptom Control in Palliative Care - 5th Edition (2013)
• Bupivacaine – Begin with 0.125% bupivacaine
(125mg in 100mls). Give 10ml statim as a bolus dose,
then run at 1-20mls per hour, starting the infusion
at 10mls per hour. With severe pain the patient may
require increased concentrations of bupivacaine (up
to 0.5% = 500mg in 100mls) run at the same rates.
• Typical Intrathecal Recipe:
• Morphine – Begin with 1/200th of the daily oral dose
(1/100th parenteral dose) up to a maximum initial
infusion of 5mg per 24 hours. For opioid naieve
patients, begin with 0.5-1mg per 24 hours. With
severe pain the morphine dose may need to be
progressively increased to 15mg per 24 hours, above
which there is a high risk of convulsions.
• Bupivacaine – Begin with 0.125% bupivacaine. Give
a 3ml bolus, then start the infusion at 2mls per
hour and run at 1-5mls per hour. A rising level of
dermatomal block indicates that the rate of infusion
is too high (easily tested by running a block of ice
over the abdomen and chest wall).
• A fall in blood pressure indicates that the infusion is
producing an effect. Most people tolerate a systolic of
85-90mm Hg.
• Be aware that pain relief may dramatically improve
requiring a sharp reduction in systemic opiates to
prevent toxicity.
Renal Failure
• Morphine: In patients with abnormal renal function
(including some elderly or cachectic people with
a normal creatinine) highly active metabolites of
morphine accumulate. Patients typically develop good
analgesia initially, but this may be followed by coma
and respiratory depression over the next 48 hours.
With so many alternate opiate options available today
morphine is best avoided in patients with an EGFR <
60mls/min. If it must be used then careful supervision
aiming initially to relieve pain, then reducing the
morphine dose by 75% (EGFR 20-60ml/min) over
the next 1–2 days to a lower maintenance level is
recommended. Extreme caution is recommended
for EGFR <20ml/min. These patients should not be
commenced on sustained-release preparations until
the steady-state morphine dose has been established
with liquid morphine.
• Hydromorphone also accumulates the parent drug and
metabolites, but these are relatively inactive compared
with morphine. It can be introduced in about half its
normal dose in patients with severe renal failure (EGFR
< 30ml/min).
• Oxycodone has no significant active metabolites but
the parent drug accumulates. It is a safer choice but
Symptom Control in Palliative Care - 5th Edition (2013)
should be used in about half the usual dosage after an
initial ‘loading dose’ for 24hours in patients with EGFR
< 30ml/min. It is recommended not to use in patients
with EGFR < 10ml/min due to high risk of excess
sedation.
• Fentanyl has no active metabolites and about 75%
is eliminated through the kidneys. It is a safe option,
though the elimination time may be increased in severe
renal failure and a lower dose may be effective. Some
authorities recommend using about 75% of the usual
dose for EGFR 10-20ml/min and half-doses for less
than this.
• Methadone has few active metabolites and is
considered by some authorities to be the drug of
choice in renal failure. However it already has complex,
unpredictable pharmacokinetics and the parent drug
can accumulate in renal failure. It is not recommended
here except under the supervision of a pain specialist
experienced in its use.
• Buprenorphine (Norspan) has no significant active
metabolites and is considered safe in renal failure
patients, although it is dialysed, which may make its
use complex in these patients.
Hepatic Failure
All the opioids are metabolized through the liver, so
may have increased bioavailablity in liver failure. This
doesn’t usually present clinical problems in patients
already stabilized on opiate analgesics, although it might
be a cause of increasing drowsiness or other toxicity in
patients with deteriorating liver function. If opiates are
introduced for patients with marked liver dysfunction,
careful introduction of lower-than-usual initial doses are
recommended (e.g. commencing 5mg of morphine orally
every 4 hours).
Intravenous Drug Users
Reluctance to prescribe adequate analgesic doses of
narcotic drugs to this group of patients is a significant
cause of morbidity. Concern about addiction should be
secondary to good symptom management, and ‘limit
setting’ used only in patients clearly misusing prescribed
regular medications.
Common Opiate Conversions
In the past, opiate conversions were mainly limited to
transferring from a weak opioid to morphine. It is much
more common these days to transfer patients from one
opioid to another. This may be for convenience, or to
avoid the side-effects of one preparation, or an attempt
to improve pain by opioid rotation. Commonly used
conversions as applied in our service are given here. It
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is emphasized that while these guidelines have reliable
clinical application they are, at best, good estimates and
there is individual variability.
Conversions are given here from different opioids to
the oral equivalence of immediate-release morphine
every four hours. The equivalent doses of long-acting
preparations could be used in place of these. To
convert between other opioids you can work back from
their morphine equivalence (eg from oxycodone to
hydromorphone, multiply by 1.5 to get the morphine
equivalence of oxycodone then divide this by 5 to get the
right dose of hydromorphone). Conversions from oral to
parenteral routes of administration are also given for the
drugs where relevant.
Converting oral to parenteral morphine
C, IM or IV morphine has equivalent effect in
• S
one-half of the oral dose. This is due to first-pass
hepatic metabolism of one-half to two-thirds of
the orally administered morphine dose. Like most
services around the world we use one-half the oral
dose when changing patients over to subcutaneous
administration.
Converting codeine to morphine
• T
wo codeine tablets (60mg) are equivalent to morphine
5–10mg (about 1/8th of the dose of codeine) every 4
hours.
Converting tramadol to morphine
• 1
00mg of tramadol is roughly equivalent to morphine
10mg orally.
Converting oral to parenteral oxycodone
• Parenteral oxycodone is now available although it is
expensive and not yet listed on the PBS. Use half the
total daily oral dose, divided into six, four-hourly SC
injections.
Converting oxycodone to morphine
• Durogesic 25 ≡ 15mg oral morphine every 4 hours
(range: 45-135mg oral morphine per 24 hours)
• Durogesic 50 ≡ 30mg oral morphine every 4 hours
(range: 135-220mg oral morphine per 24 hours)
• Durogesic 75 ≡ 45mg oral morphine every 4 hours
(range: 220-310mg oral morphine per 24 hours)
• Durogesic 100 ≡ 60mg oral morphine every 4 hours
(range: 310-400mg oral morphine per 24 hours)
• E
very subsequent increase in durogesic of 25mcg/
hour ≡ an additional 15mg of morphine every 4 hours
orally. The full range equivalences are given in MIMS
for reference.
Converting transdermal to parenteral fentanyl
• The same dose should be given by infusion (eg for
Durogesic 25, change to parenteral fentanyl in a dose
of 25mcg/hour), starting the infusion 6-12 hours after
removing the patch. If the patient becomes drowsy half
the dose of the fentanyl infusion for 6 hours or until
pain breaks through.
Converting transdermal (TD) Buprenorphine
(Norspan) to Morphine
• Every 5mcg/hr represents 2mg q4-hourly of oral
morphine
• Norspan 5 ≡ 2mg oral morphine every 4 hours
• Norspan 10 ≡ 4mg oral morphine every 4 hours
• Norspan 15 ≡ 6mg oral morphine every 4 hours
• Norspan 20 ≡ 8mg oral morphine every 4 hours
• Alternatively multiply the Norspan patch dose by a
factor of 2.4 to calculate the total daily dose of oral
morphine in mgs.
Converting methadone to morphine
• No direct conversion between methadone and other
opioids can be used. The use of methadone is covered
in more detail in the earlier section (page 5).
• U
se a conversion factor of 1:1.5 (Oxycodone 10mg is
equivalent to 15mg of morphine).
Converting hydromorphone to morphine
• U
se a conversion factor of 1:5 (Hydromorphone 1mg is
equivalent to 5mg of morphine). .
Converting oral to parenteral hydromorphone
• G
ive one-half of the oral dose.
Converting transdermal (TD) fentanyl to morphine
• E
very 25mcg/hr represents 15mg q4-hourly of oral
morphine.
• Durogesic 12 ≡ 7.5mg oral morphine every 4 hours
(range: up to 45mg oral morphine per 24 hours)
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Symptom Control in Palliative Care - 5th Edition (2013)
Gastrointestinal Symptoms
Nausea and Vomiting
• Metoclopramide: 10-20mg orally or SC, then every 4–8
hours orally or SC
The common causes of nausea and vomiting are:
• Domperidone: 10-20mg every 4–8 hours orally
• Metabolic problems
• Cisapride: 5 to 10mg every 8 hours orally (only
available through the special access scheme in
Australia). Also stimulates small and large bowel.
Reportedly synergistic when combined with
metoclopramide.
• Drug-induced
• Upper gastrointestinal inflammation
• Raised intracranial pressure
• Constipation
• Bowel obstruction
The most common is opiate-induced nausea and
vomiting. The choice of anti-emetic depends on the
cause as there are three levels where drug therapy may
be effective: 1. Chemoreceptor trigger zone (CTZ; D2
and 5HT3 receptors): haloperidol, prochlorperazine
(Stemetil), metoclopramide, ondansetron (Zofran),
tropisetron (Navoban); 2. Gastric emptying: domperidone
(Motilium), metoclopramide, erythromycin; 3. Vomiting
centre (H1 and cholinergic receptors): promethazine
(Phenergan), cyclizine, hyoscine hydrobromide (Hyoscine
injection, Kwells).
Chemoreceptor Trigger Zone Blockade
For metabolic, opiate and other drug-induced nausea:
• Haloperidol: 3mg immediately orally or SC, then 3mg
orally at night. Advantage is long half-life enabling
successful control with once-daily administration.
Depending on response, reduce to 1.5mg or increase
to 5mg nightly
for maintenance
• Prochlorperazine: 10mg every 4–8 hours orally or
25mg every 12 hours by suppository
• Erythromycin: 75mg oral elixir every 8 hours (this has
developed popularity for patients with denervated
stomachs, eg following oesophagectomy with thoracic
stomachs and gastric stasis). Combination with
cisapride is contra-indicated.
These drugs may increase colic in patients with
constipation or bowel obstruction. With upper gut
obstruction vomiting may be increased due to reverse
peristalsis, in which case this class of drug should be
withdrawn.
Vomiting Centre Blockade
The following drugs may be used in combination with
other classes of drugs in resistant cases and may be
considered first-line treatment in vomiting due to
gastrointestinal obstruction and steroid-resistant raised
intracranial pressure:
• Promethazine: 10–25mg orally or SC, then every 12
hours orally or SC
• Cyclizine: 25-50mg orally or SC, then 25-50mg every
8-12 hours orally or SC (the tablets are only available
on the special access scheme in Australia)
• Hyoscine hydrobromide: 0.3–0.6mg every 8 hours
orally or 0.2-0.4mg SC every 8–12 hours.
• Metoclopramide: 10-20mg orally or SC, then every 4–8
hours orally
Broad-Spectrum Anti-Emetic
• Ondansetron: 4-8mg orally or SC, then every 8–12
hours orally
Recommended for mechanical bowel obstruction (see
P…) where other measures have failed:
• Tropisetron: 5mg once daily orally.
• Levomepromazine 6-12.5mg PO or SC stat, then
every 6-12 hours or by continuous SC infusion
(levomepromazine is only available on the special
access scheme in Australia).
If unsuccessful, or only partially successful, add a
different class of drug to combine the effects with
increased gastric emptying or vomiting centre blockade.
Ondansetron and tropisetron may have an additive effect
when used with other drugs that act on the CTZ.
Increasing Gastric Emptying
For gastric stasis (the aetiology in 5–10% of opiateinduced vomiting) and for combination with CTZ-blocking
drugs, if needed:
Symptom Control in Palliative Care - 5th Edition (2013)
Important Points
For intractable symptoms consider:
1.Colonic faecal loading or impaction (P.R. examination,
x-ray). See page 15.
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• Hypercalcaemia. Consider treatment with oral
sodium clodronate (Bonefos), disodium pamidronate
(Aredia) 30-90mg IV, or Zoledronic acid (Zometa)
4-8mg IV.
• Upper GI inflammation. Omeprazole (Losec) 2040mg orally in the morning, or Esomeprazole
(Nexium) 20-40mg orally in the morning (may be
used twice-daily. Ranitidine (zantac) injections can
be given SC.
• Bowel obstruction. See page 16. Avoid bowel
stimulants such as metoclopramide, cisapride,
docusate sodium with senna, senna (Senokot).
• Raised intracranial pressure. Use steroids and
consider further investigation if appropriate.
2.Parenteral therapy in patients unable to tolerate oral
medications:
• Initiate treatment through the SC route using
medication options already discussed. Continue
with regular SC injections in place of the oral
regimens, or consider a syringe driver for at least 48
hours. A combination of promethazine 25-100mg
per 24 hours and metoclopramide 40-60mg per
24 hours by syringe driver is often effective for
most causes of nausea and vomiting. A small dose
of dexamethasone (0.5mg) can be added to the
infusion if local inflammation at the injection site is a
problem.
• Consider rehydration with SC fluids, using 1-2 litres
of normal saline or 4% dextrose and 1/5th normal
saline, if desirable.
Constipation and Faecal Impaction
There is a considerable range of options for the
management of these symptoms even in our local
service. The following guidelines reflect a personal
approach, which is not necessarily better than others.
The most important recipe for success however is to have
a systematized approach that includes regular review
and sensible medication changes if required, using
faecal softeners, bowel stimulants, contact evacuants or
‘flushing’ agents, with or without rectal measures. One
important introduction in recent years has been macrogol
3350 (Movicol, Osmolax), which has considerably
reduced the need for rectal measures in our service.
A further development recently has been the
introduction of methylnaltrexone injections (Relistor)
given subcutaneously for opiate-induced constipation.
Prophylaxis When Commencing Regular Opiates
It is recommended that all patients on opiate treatment
receive prophylaxis, even when reporting ‘normal’ bowel
habit.
Page 14 - click to return to contents
The following stepwise approach is recommended:
1.Docusate sodium with senna (Coloxyl with Senna) or
bisacodyl (Durolax): 2 tablets at night (Bisacodyl is
available through the PBS in Australia). If effective,
continue with this and consider reducing the dose if it
causes abdominal pain or diarrhoea. If ineffective by
3rd day, go to the next step.
2.Glycerine, bisacodyl (Durolax) or docusate plus
bisacodyl (Coloxyl) suppository immediately. Increase
docusate sodium with senna or bisacodyl to 2-3 tablets
twice-daily. If ineffective by 2nd day, go to the next
step.
3.Substitute oral macrogol 3350 (Movicol 2-4 sachets; or
Osmolax 3-6 level scoops) in the morning or at night.
As a bowel flushing agent it would seem rational to use
macrogol 3350 once daily rather than in divided doses.
Some patients who dislike the taste or feel nauseated
on Movicol appear to tolerate Osmolax better,
although treatment may need to be discontinued.
Movicol can be given in a dose of 8 sachets daily (or
Osmolax 12 scoops daily) for up to 3 days to treat
faecal loading or impaction (see below). If ineffective
after the 2nd day, increase the dose or go to the next
step.
4.Repeat suppository and/or phosphate enema if
required. Try liquid paraffin (Agarol) or lactulose
(Duphalac, Actilax) 20-30mL plus senna granules 1-2
teaspoons twice to three times daily. Alternatively try a
different bowel flusher – Epsom salts 1-3 teaspoons in
the morning.
5.Some patients are resistant to all these measures and
require the combined use of oral aperients and rectal
measures, using suppositories every 2-3 days and/or
enemas once or twice a week.
Evaluation of the Constipated Patient
The following steps are recommended:
• Take a history of duration, extent and nature of
constipation including whether stool is hard, soft or
spurious (diarrhoea)
• Abdominal examination to detect colonic loading.
Rectal examination to determine whether stool is hard
or soft, impacted or not impacted. Dilated rectum
suggests high colonic loading or impaction. A lax anal
tone suggests a neurological problem, such as disease
affecting the cauda equina.
• Obtain x-ray when extensive faecal loading is
suspected
• Proceed to digital disimpaction of the rectum if
indicated following adequate analgesia and sedation
(e.g. midazolam [Hypnovel] 2–5mg plus an opioid, both
by SC or IM injection).
Symptom Control in Palliative Care - 5th Edition (2013)
Management of Severe Constipation with High
Colonic Loading
For high colonic loading with ‘hard’ faeces in rectum,
the following stepwise approach may be followed:
1.Softening regimen avoiding bowel stimulants: e.g.
daily Microlax enemas plus oral liquid paraffin 30mL
3 times daily; or docusate sodium (Coloxyl 120mg
tablets) 240mg 3 times daily; soap and water enemas
100-200mL daily for 2 days.
2.Try macrogol 3350 as a bowel flusher. The
recommended dose for patients with colonic loading
is Movicol 8 sachets a day (Osmolax 12 level scoops a
day) for up to three days. This may sometimes result in
distressing faecal incontinence so it is recommended
here to initially trial a dose of Movicol 4 sachets
(Osmolax 6 scoops) in the morning. Subsequent
dosing will depend on the response. It is not
uncommon to give 8 sachets a day without response
for the first day or two, then have the passage of
normally formed stools on subsequent doses. If no
response or patient unable to tolerate the Movicol
(some of these patients tolerate Osmolax well) go on
to the next step.
3.As an alternative second or third step for patients with
opiate-induced constipation trial methylnaltrexone
(Relistor) by SC injections (see MIMS for doseage
and precautions in hepatic and renal failure). This
could be administered daily to 2nd –daily according
to response, and can be combined with the other
approaches if desired (eg 2nd-daily PRN).
4.Evacuant washouts: continue paraffin or docusate
sodium orally. Soap and water enemas 200-500mL
daily for 2 days (give up to 1 litre if volume easily
passed). Hyoscine butylbromide (Buscopan) 20mg IM
injection may be given to prevent colic. Midazolam
2–5mg IM injection may be required for sedation.
Repeat x-ray following this to check radiological
clearing (ideally).
up to 1litre of enema solution if well tolerated. Repeat
x-ray following this to check for radiological clearing
(ideally).
2.As an alternative for patients with opiate-induced
constipation, trial methylnaltrexone (Relistor) by SC
injections (see MIMS for doseage and precautions in
hepatic and renal failure). This could be administered
daily to 2nd –daily according to response, and can be
combined with the other approaches if desired (eg
2nd-daily PRN with daily Movicol).
3.After success, commence aperients following review
of previous (failed) aperient regimen (see page 14 on
prophylaxis). Use maintenance Movicol 1-2 sachets or
Osmolax 2-3 level scoops in the morning if this was
effective and well tolerated.
For high colonic loading with an ‘empty’ rectum on
P.R.:
1.Evacuant washouts: Movicol/Osmolax as described
above. Alternatively Epsom salts 1-3 teaspoons in the
morning. Failing this try oral liquid paraffin 30mL 3
times daily or docusate sodium tablets 240mg 3 times
daily plus soap and water enema 500mL–1 litre daily
for 3 days. Repeat x-ray to check radiological clearing
(ideally).
2.As an alternative for patients with opiate-induced
constipation trial methylnaltrexone (Relistor) by SC
injections (see MIMS for doseage and precautions in
hepatic and renal failure). This could be administered
daily to 2nd –daily according to response, and can be
combined with the other approaches if desired (eg
2nd-daily PRN).
3.After success, commence aperients following review
of previous (failed) aperient regimen (see page 14 on
prophylaxis). Use maintenance Movicol 1-2 sachets or
Osmolax 2-3 level scoops in the morning if this was
effective and well tolerated.
Notes
5.After success, commence an aperients regimen,
which must be more aggressive than previous (failed)
aperient regimen (see page 14 on prophylaxis). If the
macrogol 3350 flushing approach succeeded then it is
often easy to maintain on 1-2 sachets Movicol (or 2-3
scoops Osmolax) every morning or night plus or minus
coloxyl with senna.
• High volume soap and water washouts: slow
administration over 20 minutes via rectal tube may be
needed in patients who have recto-sigmoid spasm
and ‘flush-back’ effect. This administration can be
managed by setting up an infusion with IV stand.
Spasm may be prevented by prior administration of
hyoscine butylbromide 20mg by IM injection.
For high colonic loading with ‘soft’ faeces in rectum,
the following steps are recommended:
• Perseverance is the key to success in difficult cases. For
example, soap and water enemas 500ml-1 litre daily for
7 days is sometimes needed (patient is invited to call
‘rest days’).
1.Evacuation: Try Movicol or Osmolax as described
above. Failing this use liquid paraffin 30mL 3 times
daily or docusate sodium tablets 240mg 3 times
daily, and soap and water 200-500mL plus bisacodyl
enema (Bisalax) 10mL (mixed) daily for 3 days. Give
Symptom Control in Palliative Care - 5th Edition (2013)
• These approaches may be inappropriate in the last
days of life when bowel management should be
dictated by symptoms and common sense.
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Medical Palliation of Bowel
Obstruction
• Add 0.5mg of dexamethasone (as the last) to the
infusion if there are problems with SC-site inflammation
due to promethazine.
Surgical Palliation
• Commence octreotide (Sandostatin) 0.1-0.5mg SC
every 8 hours, which can be added to the syringedriver as a 24-hour infusion, plus dexamethasone
8mg SC daily in patients with persistent high volume
vomiting or where you suspect vomiting will be difficult
to manage.
This should be considered first. Generally surgical
palliation is the best form of management of bowel
obstruction under the following conditions:
• A fit and willing patient
• A single site of obstruction or a potentially reversible
cause.
Modern stenting techniques should be considered for
patients with proximal obstruction of the duodenum or
gastric outlet where appropriate and not in the terminal
phase. Otherwise medical palliation should be the
approach.
Principles of Medical Palliation
• Avoid ‘drip and suck’ (unless considering surgery)
• Eliminate nausea and vomiting using antiemetics.
Some patients may continue to experience vomiting
once or twice a day in the absence of nausea
• With high volume secretions reduce volume with
octreotide (consult with your local palliative care
services)
• Add levomepromazine 6.25mg SC statim, followed
by 25-50mg SC infusion over 24-hours in resistant
cases. This drug can be used in higher doses if terminal
sedation is desirable for people who are dying.
The author has combined this drug with the other
drugs mentioned above in the same syringe-driver.
Levomepromazine is only available through the special
access scheme in Australia.
• Alternative anti-emetics include:
• Cyclizine 25mg SC statim, then 50-150mg by
SC infusion over 24 hours. Only accessible by
the special access scheme in Australia and less
compatible with Buscopan in a syringe-driver than
promethazine. Considered the drug of choice in
many centres.
• Eliminate colic using antiperistaltic drugs
• Hyoscine hydrobromide 0.3mg sublingually every 8
hours
• Use enemas to reduce low obstruction if possible
(especially with subacute bowel obstruction)
• Hyoscine hydrobromide 0.2-0.4mg by SC injection
every 8–12 hours
• Reduce peri-tumour oedema with corticosteroids.
• Prochlorperazine suppositories 25mg every 8–12
hours
• Encourage ambulation, eating and drinking.
• Continue current oral opiates in half dose
subcutaneously
Management of Nausea and Vomiting
My preference is to use promethazine and
metoclopramide in combination despite the possibility of
increasing the vomiting of high small bowel obstruction
with metoclopramide due to reverse peristalsis. This
is rare in practice, especially where steroids are used
concurrently, and the stimulant effect of metoclopramide
can overcome functional or partial obstructions, and
eliminate gastric stasis. These orders
• Give promethazine 25mg SC statim, then 50mg
SC infusion over 24 hours plus metoclopramide
10mg SC statim, and 40mg by SC infusion over 24
hours (or promethazine 25mg SC, twice daily plus
metoclopramide 10mg SC every 6 hours). These
drugs can be mixed in a syringe driver with hyoscine
butylbromide (Buscopan [colic]) and morphine or
hydromorphone (pain).
Page 16 - click to return to contents
• Haloperidol 1-3mg subcutaneously every 8 hours (or
combined in the syringe-driver)
Patients should remain free of nausea but may still
vomit once or twice a day. This is worth explaining to
the patient and family. Some patients require continual
parenteral treatment, while others may be subsequently
managed using the same drugs orally. Some patients
have repeated episodes of acute obstruction that can
be well-managed at home with a few days of treatment,
avoiding repeated episodes of hospitalization. Good
planning with available drugs in the household and
written orders for nurses to follow are required for this.
The availability of subcutaneous fluids, eg 1L normal
saline given over 4-6 hours every 24 hours, may also be
needed.
Management of Colic
• Discontinue all stimulant aperients: i.e. docusate
sodium with senna; senna; bisacodyl
• Consider docusate sodium tablets 240mg or liquid
paraffin 30mls every 8 hours as a faecal softener after
Symptom Control in Palliative Care - 5th Edition (2013)
controlling vomiting. Commence in all patients with
subacute (incomplete) bowel obstruction
• Determine the level of obstruction: gastroduodenal,
proximal or distal small bowel, large bowel. There is
often no colic with high bowel obstructions.
• For faecal colonic loading or impaction follow the
evaluation steps on page 15. This is a common cause of
presentations with large bowel obstruction, even when
a significant organic component is present
week. Some patients require high volume soap and
water enemas (up to 1L) once or twice a week.
• Continue appropriate antiemetic regimen as described
above.
• Consider reducing obstruction by using
dexamethasone. If desirable, commence 8mg daily
for 5 days and, if of benefit, continue on 2-4mg daily.
I have often found this to be essential and symptoms
can respond well but return as the steroid dose is
reduced necessitating continuing high-dose steroids.
• Initial parenteral treatment: hyoscine butylbromide
20mg IM and parenteral morphine 5–10mg IM or
SC (in patients already on morphine give 1/12th the
daily oral dose parenterally) followed by hyoscine
butylbromide 20mg every 4-8 hours SC (the daily dose
may be given as continual SC infusion by syringe driver,
combined with other drugs as described above). Long
term parenteral maintenance may be required in some
patients.
This condition may not respond effectively to measures
outlined above, particularly in relieving vomiting. The
following treatments are recommended:
• Once vomiting is controlled, any of the following
oral antispasmodics may be employed long-term if
continuing treatment is required:
• Dexamethasone 8mg SC daily may relieve obstruction
by reducing tumour-induced inflammation. Give a 3-5
day clinical trial
• Lomotil 2.5–5mg every 8–12 hours (a personal
favourite with little anticholinergic effect)
• Mebeverine (Colofac) 135–270mg every 8 hours (no
anticholinergic side-effects)
• Hyoscine hydrobromide 0.3mg sublingually every
8-12 hours
• Hyoscine butylbromide 10-20mg every 6 hours (may
not work due to low bio-availability when given
orally)
• Donnatab 1-2 tablets every 6-8 hours.
• Propantheline (Pro-Banthine) 15-30mg every 6 hours.
Maintenance Therapy in Patients with Subacute
Bowel Obstruction
These patients have partial organic obstruction and
require colic prevention whilst maintaining a regular
soft stool. Existing faecal loading or impaction should
be managed in accordance with the steps given on
page 15. Care must be taken where the degree and
level of organic obstruction is uncertain. Endoscopy or
radiocontrast studies may be indicated. For management
after treating the initial presentation, the following is
recommended:
• Lomotil 2.5–5mg plus docusate sodium 240mg every
6–12 hours. From personal experience this surprising
combination frequently results in a colic-free patient
passing normal stools. Movicol 1-2 sachets daily can be
added. Glycerine, coloxyl or bisacodyl suppositories
to be used if required every 2–3 days. Soap and water
enemas 100–500mL may be needed once or twice a
Symptom Control in Palliative Care - 5th Edition (2013)
Gastroduodenal and High Small Bowel Obstruction
• Remove metoclopramide from the treatment above in
patients not responding in case it is causing reverse
peristalsis against an organic obstruction.
• Octreotide (Sandostatin) 0.1-0.5mg every 8 hours SC
will reduce the volume of intestinal secretions and
improve vomiting in most patients. Consider a 3–5day trial in distressed patients who wish to avoid a
nasogastric tube or ‘venting’ gastrostomy.
• Consider a nasogastric tube or gastrostomy to relieve
vomiting in patients who do not respond to the
measures outlined above, assuming that they are fit
and willing.
• Dehydration is desirable in terminally ill patients due
to reduction in volume of intestinal secretions. IV fluids
are particularly contraindicated in this group as they
will increase vomiting and lead to a more unpleasant
death.
• Consider SC fluids to maintain hydration in other
patients, usually around 1-2 litres a day but lean
towards ‘the dry side’.
Squashed Stomach Syndrome
This condition is characterised by dyspeptic symptoms
associated with compression of the stomach from
hepatomegaly or an upper abdominal tumour. Symptoms
are:
• Fullness
• Early satiety
• Epigastric pain
• Flatulence
• Nausea
• Vomiting
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• Heartburn
• Hiccups.
Treatment is as follows:
• Antiflatulent: Mylanta 10mL every 4–6 hours;
simethicone (Degas, Gasbusters) 100-200mg with
meals or every 6 hours.
• Acid reduction: Omeprazole 20-40mg in the morning;
esomeprazole 20-40mg in the morning.
• Increase gastric emptying: Metoclopramide 10–20mg
every 4–8 hours; domperidone 10-20mg every 6 hours.
• Dietary advice regarding small meals.
Anorexia
This is a common and sometimes distressing symptom
in people with advanced cancer or in other terminal care
situations often associated with weakness, decreased
energy and low well-being. Therapeutic options include:
• Dexamethasone 4mg daily, discontinue after 5 days
if no effect. Reduce the dose to a minimal effective
level where there is a good response. Dexamethasone
may also enhance well-being, strength and energy.
Dexamethasone may not be appropriate in patients
with a life expectancy beyond 2 or 3 months due to
progressive side effects including the potential to
cause proximal myopathy.
• Central suppression of hiccup reflex: chlorpromazine
(25–50mg then 25mg every 8 hours orally).
Chlorpromazine 25mg IV may be used in a distressed
patient
• Other: nifedipine (Adalat) 10mg orally or sublingually
then 10-20 mg every 12 hours; there have been reports
of using benztropine, which has the advantage of SC
administration, although I have no local experience
with this.
Options for Maintenance Treatment
• Baclofen (Clofen, Lioresal) 5mg three times a day
increasing to 10-20mg three times a day if required.
• Correction of gastric distension: metoclopramide
(10–20mg every 4–8 hours) plus antiflatulent (e.g.
Mylanta 10mL every 4–8 hours or simethicone 100200mg every 6 hours)
• Central suppression of hiccup reflex: chlorpromazine
10–25mg every 8 hours orally
• Suppression of central irritation from intracranial
tumour: dexamethasone 16mg daily reducing to
4–8mg maintenance, sodium valproate 500–1000mg at
night and phenytoin (Dilantin) 200–300mg daily
• Other: nifedipine 5-20mg every 12 hours orally or
sublingually.
• Megestrol acetate (Megostat) 160mg –800mg daily
(may require the largest dose to be effective [5 tablets])
• Amitriptyline 10–50mg at night
• Cyproheptadine (Periactin) 4mg every 8 hours.
Hiccups
Hiccups are likely to be caused by one of the following:
• Gastric distension
• Diaphragmatic irritation
• Phrenic nerve irritation
• Brain tumour
• Infection.
Stopping the Attack
• Baclofen (Clofen, Lioresal) is a personal preference,
although it can be sedating or cause postural
hypotension even in small doses. Start with 10mg orally
then 5mg three times a day.
• Reduce gastric distension: metoclopramide (20mg
orally or SC) plus antiflatulent (e.g. Mylanta 20mL or
simethicone 200mg)
• Pharyngeal stimulation: swallow 2 heaped teaspoons
of granulated sugar or 2 glasses of a liqueur; drink from
‘wrong’ side of a cup
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Symptom Control in Palliative Care - 5th Edition (2013)
Respiratory Symptoms
Breathlessness
In patients where death is not imminent, with recently
developed or increasing dyspnoea, appropriate
investigation and treatment of an underlying cause may
be worthwhile. Underlying causes of breathlessness
include:
• Bronchospasm
• Cardiac failure
• Pulmonary infection
recommendation here is to use morphine if it is well
tolerated and to reserve other agents for patients who
have undue side effects or allergy.
Use of Anxiolytics
Many patients with dyspnoea have related anxiety
and a feeling of panic, particularly when intermittent
acute attacks occur. Fear of a suffocating death is often
present. The following approaches can be usefully
combined with morphine at the outset of treatment:
• Anaemia.
• Chlorpromazine 10–50mg at night or promethazine
12.5–25mg twice daily. The literature reports that these
agents may have a significant effect of reducing the
symptom of dyspnoea whereas benzodiazepines do
not. In clinical experience though benzodiazepines are
useful adjuncts, relieving anxiety or panic when given
with an opiate.
• Chronic airways limitation (CAL)
• Diazepam (Valium) 2–10mg at night.
Use of Morphine
• Lorazepam (Ativan) 0.5-1mg sublingually during an
attack of dyspnoea and panic can be very effective. Its
availability with written instructions to administer this
with a breakthrough dose of opiate will give the family
confidence in managing this situation. The dose can be
carefully titrated up to 2.5mg sublingually PRN if a 1mg
dose is ineffective. Regular lorazepam 0.5-1mg every
8-hours can be prescribed for patients with anxiety in
this setting.
• Pleural effusion
• Superior vena cava obstruction (SVCO)
• Pericardial effusion
• Lymphangitis carcinomatosis
• Low dose regular oral morphine is usually effective
in relieving dyspnoea. With careful titration of the
dose, there is little or no risk of shortening life through
respiratory depression, assuming the patient does not
have renal failure or CO2-retention. In patients with
renal failure, select hydromorphone (Dilaudid oral
liquid) in 1/5th the recommended morphine doses
below.
• In patients without pain, commence 2mg (1mg in
elderly patients or those at risk including COPD
patients with CO2-retention) every 4 hours, increasing
the 4-hourly dose by 2mg daily until relief or
drowsiness is achieved. It is unusual to require more
than 5–10mg every 4 hours.
• In patients with pain, morphine will have little
benefit on dyspnoea until adequate analgesia has
been achieved. This usually requires appropriate
combination of morphine and other analgesic
medications as described in the section on Pain
Control (page 2). Following this, an incremental 25–
50% increase in the morphine dose above its analgesic
dose is recommended for control of dyspnoea.
Use of other Opioids
• The availability of multiple opioids (morphine, fentanyl,
hydromorphone, oxycodone, buprenorphine and
methadone) has led to some discussion as to the
relative value of these in comparison to morphine.
There is no convincing evidence that they are different
from one another in the management of dyspnoea. The
Symptom Control in Palliative Care - 5th Edition (2013)
• Alprazolam (Xanax) 0.25-1mg sublingually during an
attack of dyspnoea and panic can be very effective (as
for lorazepam above). Regular alprazolam 0.25-1mg
every 8-hours can be prescribed for patients with
anxiety in this setting.
• Clonazepam (Rivotril) oral liquid 0.25-1mg sublingually
during an attack. This has a long half-life and may
accumulate with drowsiness if used regularly. However
it has the advantage of coming in liquid form as many
patients with dyspnea have dry mouths.
Counseling and reassurance of the patient that
breathlessness can be relieved and that they will not
be allowed to ‘suffocate’ in the terminal phase can give
great relief to many patients who have experienced acute
attacks of dyspnoea in the past.
Use of Oxygen
Most patients should not require continuous oxygen
where there has been optimal management with
morphine and anxiolytics. A recent study has shown
that a high-pressure electrical, hand-held fan is equally
click to return to contents - Page 19
effective in the management of dyspnoea for patients
without low oxygen saturations. While emphasis is on
proper symptomatic management oxygen should be
available at home in the following settings:
• Where acute attacks are likely – e.g. in end-state
COPD, cardiac failure or thromboembolism
• Where the patient remains extremely anxious despite
efforts to counsel and control symptoms
• When there is geographical isolation from after-hours
medical and nursing services.
Parenteral Approaches in Terminal, Breathless
Patients
For acute or distressing dyspnoea in the dying patient:
• Give morphine SC, IM or IV with clonazepam (Rivotril)
2mg sublingual, or midazolam 5–10mg SC, IM or IV.
The dose of morphine depends on the patient’s usual
oral or SC dose but is often 30mg or more
• Establish a continual SC infusion of morphine +
midazolam 30–60mg every 24 hours, or morphine +
clonazepam oral liquid 2mg sublingually every 4-6
hours, with the aim of keeping the patient asleep
and asymptomatic. (Other medications should be
continued by alternative routes to oral administration,
see page 27). The recommended initial morphine dose
is 30mg over 24 hours; or 2 times the total 24-hour
dose that was being administered parenterally (or
the same dose that they were receiving orally) prior
to deterioration. The morphine equivalence of other
opioids is covered on page 11
• If adequate sedation (i.e. sleep) is not achieved, see
page 24.
orally every 4 hours. In patients with neuromuscular
conditions who have hypoventilation and CO2retention consideration of positive flow ventilation
in the context of opiate use might be appropriately
considered in consultation with respiratory services.
• If the patient experiences acute breathlessness, the
prognosis of these conditions may be better than with
terminal cancer but decision-making is more complex.
Options include:
• Intensify medical management with full investigation
of the reasons for deterioration
• Management as for a dying patient as outlined
above
• An approach that is intermediate between the first
two options which involves intensification of medical
investigation and treatment, while concurrently
increasing the doses of morphine and anxiolytics.
This gives a ‘window’ for recovery while ensuring a
patient considered to be ‘probably dying’ can do so
comfortably, avoiding a very distressing respiratory
death.
• Patient and family involvement with these options
and decision-making is important, particularly in
anticipating and respecting the patient’s wishes
should deterioration take place.
Cough
In the fittest of patients, consider treatable options rather
than solely depending on suppressive therapy. Such
options may include:
• Mucolytics for inspissated sputum
• For subacute or progressive dyspnoea in the terminal
patient, in association with agitation, delirium or
distress, the above approaches are recommended. The
addition of haloperidol 2-5mg SC statim then 2-10 mg
in the infusion is also recommended for delirium. It is
appropriate to provide heavy sedation if the patient
requests it in this setting.
• Treatment of gastro-oesophageal reflux
Dyspnoea Associated with End-stage Non-Malignant
Pulmonary Diseases (including COPD) or End-stage
Cardiac Failure
• Treatment of cardiac failure
• When symptoms are limiting despite optimal therapy,
management with morphine and anxiolytics as
described above is both safe and appropriate in most
patients with normal renal and hepatic function. Care
should be taken with patients at high risk of developing
or increasing CO2 retention including those with COPD
and neuromuscular conditions affecting respiration.
It would be judicious to commence treatment at the
lowest dose ranges and titrate until the desired effect
is produced, e.g. starting with morphine 0.5-1mg
Cough suppression is indicated in all patients with
persistent symptoms.
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• Antihistamines or steroid nasal sprays for post-nasal
drip
• Antibiotics for chest infection
• Bronchodilators for bronchospasm
• Stopping (or substituting for) ACE inhibitors
• Radiotherapy, chemotherapy or corticosteroids to
modify pathological processes.
Suppressing Cough
The following options are available to suppress cough:
• Reduce pharyngeal stimulation using e.g. Simple
Linctus 10mL every 2–4 hours
• Central suppression of the cough reflex using narcotic
medications such as codeine phosphate 30–60mg
every 4 hours (or as Codeine Linctus), Linctus
Symptom Control in Palliative Care - 5th Edition (2013)
Pholcodine (Durotuss forte) 5-10mls every 4-6-hours
or morphine 2–20mg every 4 hours. If already taking
morphine, try a 25–50% increase in dose and titrate
against drowsiness. The same applies to using
alternative opiates to morphine with oxycodone and
hydromorphone being the most accessible options in
appropriate doseage (see morphine equivalent doses
on p…). Select hydromorphone in patients with renal
failure and EGFR<60mls/min. As a personal approach
I often mix linctus pholcodine with the stronger opioid
to keep the benefit of the syrup-effect of the linctus.
• Paroxetine (Aropax) 5-20mg has been reported to be
very effective though its site of action is unknown.
• Methadone: some authorities advocate methadone
as a better opiate for cough-suppression. Evidence
for this is limited but it’s worth a trial in difficult cases.
Commence 2.5-5mg every 6-hours for 24 hours then
reduce dose to 12-hourly (this can be added to the
patients other opiate regimen, although drowsiness
and a long sleep has been reported with the first dose).
The dose can be escalated according to effect but
should only be changed at weekly intervals in 25-50%
steps. Excessive drowsiness on methadone will take
24-hours to settle and doses should be omitted for this
time then recommenced in half the dose.
• Local anaesthetic blockade of cough receptors may
be used in patients whose symptoms persist despite
central suppression. Options include: lignocaine 2%,
5mL by nebuliser every 4-12 hours or bupivacaine
0.25%, 10mL by nebuliser every 4-12 hours. Only one
or two doses a day may be required when effective.
Mechanical cough receptors at the level of the carina
will be blocked with standard nebuliser. If symptom
control is not achieved, an ultrasonic nebuliser (e.g.
Bird nebulizer) can produce a smaller particle size that
will additionally block chemical cough receptors in
bronchioles. Patients should be advised not to eat or
drink for an hour following the treatment as they may
be at risk of aspiration.
• Dry secretions, if indicated, with amitriptyline 10–50mg
at night, hyoscine hydrobromide 0.2-0.4mg every 4
hours SC, hyoscine butylbromide 20mg SC initially,
then 40mg SC per 24 hours (this avoids the sedative
effects of hyoscine hydrobromide), or glycopyrrolate
(Robinul) 0.2-0.4mg initially, then 1.2-2.4mg by SC
infusion per 24 hours (also avoids sedative effect of
hyoscine hydrobromide).
• Dexamethasone 8mg orally daily for 5 days, reducing
to 4mg daily as maintenance, may be a useful adjunct
in patients with lymphangitis carcinomatosis or upper
airways compression.
Haemoptysis
Haemoptysis may be controlled with any of the following
approaches:
Dexamethasone: 8mg orally or SC daily for 3 days,
reducing to a maintenance of 2-4mg daily if desirable.
• Radiotherapy in a single palliative fraction.
• Tranexamic acid (Cyclokapron): Complex dosing refer to product information. Typical prescribing - 1g
orally every eight hours, continuing for 48 hours
after bleeding stops. Repeat for further episodes. A
maintenance dose might be desireable if bleeding
keeps returning, in which case aim for 500mg every
eight hours.
Death Rattle
This describes the rattling noise produced during
respiration, when secretions are retained in large airways,
in patients too weak to expectorate effectively.
Patients are often moribund and unaffected but
relatives, other patients and staff may be distressed by it.
Counseling relatives is usually advisable to reassure them
that the patient is not suffering. The treatment described
below is mainly preventive and should be initiated at the
first sign of respiratory noises in an unconscious patient.
Treatment
Any of the following treatment options may be
considered:
• Hyoscine hydrobromide 0.4mg every 4 hours SC, or
1.2-2.4 mg by continuous SC infusion after an initial
dose of 0.4mg.
• Hyoscine butylbromide 20mg SC initially, then 2040mg SC infusion per 24 hours.
• Glycopyrrolate 0.4mg SC initially, then 1.2-2.4mg
SC infusion per 24 hours (same dosing as hyoscine
hydrobromide)..
• Midazolam or clonazepam may be added as outlined
on page 24 if patient is agitated or restless
• If the symptom is severe, administer midazolam or
clonazepam, tilt the foot of the bed and position the
patient to achieve postural drainage.
• If associated with purulent sputum consider a
statim subcutaneous injection of Ceftriaxone (1g
reconstituted in 3.75 mls 1% lignocaine, administering
half at two separate sites).
Radiotherapy in a small, single fractionated dose may
stop cough in lung cancer.
Symptom Control in Palliative Care - 5th Edition (2013)
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Urinary Symptoms
Frequency and Urgency
Bladder Spasm
Treatable causes should be considered, including:
This is usually experienced as painful spasm in the lower
abdomen in a catheterized patient. Leaking around an
indwelling catheter is a sign of bladder spasm. Treatable
causes should be considered. These include:
• Bladder outlet obstruction, irritation or compression by
pelvic tumour:
• TURP for prostatomegaly
• Dexamethasone 8mg daily for 5 days followed by
4mg maintenance where pelvic tumour is implicated.
• Chemotherapy or radiotherapy may be options
• Infection
• Diuretic therapy
• Oversedation
• Infection requiring antibiotics, with change
of indwelling catheter or using intermittent
catheterisation every 4–6 hours
• Catheter irritation requiring reduction in balloon
volume
• Catheter sludging requiring bladder washouts or
continuous irrigation.
• Polyuria which will not respond to the treatment
options outlined below (check BSL in patients on
steroids).
Treatment
Treatment
• Effective analgesia with NSAID such as naproxen
250–500mg every 12 hours + morphine if required
every 4 hours titrated upward until there is effective
relief of pain or the occurrence of drowsiness
Treatment options include the following:
• Ural sachets (urgency): 1-2 orally, four times a day
• Cranberry juice or tablets for urgency (available in most
pharmacies): Adjust dose to response.
• Anticholinergic drugs:
• Amitriptyline 25–50mg, orally, at night is
recommended. It often markedly improves nocturia
and has additional hypnotic and anxiolytic benefits.
In patients with outflow obstruction, start in a
lower dose and increase after 48 hours, then it will
generally not lead to urinary retention.
Treatment options include the following:
• Anticholinergic drugs:
• Amitriptyline 10–50mg at night is recommended
• Oxybutynin hydrochloride (Ditropan) 5-10mg orally
every 12 hours (2.5mg nocte-q12-hourly in the
elderly or debilitated).
• Propantheline 15-30mg every 6-8 hours.
• Hyoscine hydrobromide (Kwell’s) 0.3mg every 8–12
hours sublingually
• Propantheline 15-30mg every 6-8 hours, orally
• Hyoscine hydrobromide 0.2–0.4mg every 8–12 hours
SC
• Oxybutynin hydrochloride (Ditropan) 5-10mg orally
every 12 hours (2.5mg nocte-q12-hourly in the
elderly or debilitated).
• Hyoscine butylbromide 10–20mg every 8–12
hours SC (avoids sedative action of hyoscine
hydrobromide)
• Sympathomimetics:
• Terbutaline (Bricanyl elixir) 15ml every 8 hours, orally
• NSAID
• Choice depends on prescriber-preference. May
aggravate or cause haematuria in patients with
a genito-urinary malignancy. Potentially contraindicated in renal failure.
• Non-drug measures including regular time-contingent
voiding (every 1–3 hours), ready availability of bottle,
bedpan or commode, proximity to toilet and a rapid
nursing response time.
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• Nerve blocks
• Lumbar sympathetic block
• Inferior hypogastric plexus block
• Catheter change
• For catheter leakage insert a smaller gauge catheter
to reduce bladder spasm
Hesitancy
Consider treatable causes including:
• Withdrawal of drugs with anticholinergic side effects
Symptom Control in Palliative Care - 5th Edition (2013)
• Opiate induced hesitancy may respond to changing
the opiate, and is often relieved by co-prescribing
prazosin (see below).
• Assisted posture where there is difficulty voiding lying
down
• Prostatomegaly.
• Loaded rectum
Treatment
Treatment options include the following:
• Prazosin (Minipress) 0.5–1mg once or twice daily. Mode
of action is sympathetic antagonism, which promotes
voiding
• Terazosin (Hytrin) 1mg daily for 4 days, 2mg daily for
7 days then 5mg daily if increased dose is required.
Maintenance of 5-10mg daily. Same mode of action
as prazosin but more expensive in Australia unless the
patient is a war veteran on the RPBS scheme.
• Tamsulosin (Flomaxtra) 400mcg once daily. Same
mode of action as prazosin but also more expensive
unless the patient qualifies for the RPBS scheme.
• Bethanechol (Urocarb) 10–30mg every 8-12 hours
orally or sublingually. This is a cholinergic drug that
may be used synergistically with prazosin
• Pyridostigmine (Mestinon) 60–120mg every 6–8 hours,
or the long-acting preparation 180-360mg once
daily. This drug exerts an anticholinesterase effect
and results in a generalised cholinergic response. It is
usually prescribed for myasthenia gravis and I have no
personal experience in using it for urinary hesitancy.
• Permanent or intermittent catheterisation.
Haematuria
The following approaches are frequently effective:
• Tranexamic acid: Complex dosing - refer to product
information. Typical prescribing - 1g orally every 6-8
hours, continuing for 48 hours after bleeding ceases.
Repeat process if bleeding returns. A continual
maintenance dose may be required in which case aim
for 500mg every 8 hours. Use a smaller dose 500mg
every 8-hours in patients with EGFR10-30mls/min;
and 500mg every 12-hours for EGFR<10mls/min. This
may dramatically improve bleeding though there is
a reported risk of clot retention in the ureter with
heavy renal bleeding, or of hard clots remaining in the
bladder. We have used tranexamic acid frequently in
this setting without encountering these problems so
far.
• Bladder irrigation for severe bleeding and clots.
Symptom Control in Palliative Care - 5th Edition (2013)
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Delirium, Agitation, Restlessness,
Twitching and Fitting
Assessment
It may be appropriate to exclude or manage reversible
organic factors that cause acute brain syndrome and
delirium. This is especially important in a patient who
had been functioning well before a rapid change. Such
factors include:
• Sepsis: especially urinary, respiratory, cellulitis,
infected ulcers
• Metabolic factors – hypercalcaemia, hypoglycaemia,
hyponatraemia, renal failure with obstructive uropathy,
liver failure with biliary obstruction
• Drug reactions and interactions (e.g. recently
introduced benzodiazepines)
• Urinary retention
• Inadequate pain control.
The physician needs to determine who is being adversely
affected by the restlessness or agitation, which will
involve discussion with:
• The patient – if possible
• The family – who are often greatly distressed and will
probably support immediate sedation of the patient
• The nursing staff – to assess if the patient’s condition is
distressing other patients and/or making their proper
care impossible.
It is also important to determine the severity of distress
and the level of co-operation that may be expected from
the patient. Patients may fight if held down and given
parenteral medication when they may have taken oral
medicine easily.
Severe Agitation or Restlessness
in the Terminal Phase
The aim here is to induce and maintain hypnosis.
Parenteral treatment by subcutaneous administration of
midazolam or sublingual clonazepam (Rivotril oral liquid)
are the preferred options for first-line management.
Levomepromazine or phenobarbitone sodium may be
added by subcutaneous injection if the benzodiazepines
have limited benefit. Co-prescribing haloperidol 2-5mg
S/C statim, then 2-10 mg S/C daily is recommended
where delirium is apparent or suspected.
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The approaches outlined here have been developed
regionally and are commonly applied. The use of
phenobarbitone as a second line of treatment in patients
failing to settle on midazolam and clonazepam has been
developed locally in the recommended doses and is
favoured over levomepromazine in our area.
First-line Treatment Options
• Midazolam: Statim dose 5–10mg SC or IM repeated in
30 mins, if necessary, and followed by 30–90mg every
24 hours given by continued SC infusion via a syringe
driver. Midazolam is miscible with morphine, hyoscine,
haloperidol or metoclopramide in a syringe driver. It
has a short duration of action (2 hours), which leads to
unreliable efficacy when given by intermittent 4-hourly
injection, unless given in high dose.
• Clonazepam drops (oral liquid): Statim dose 2mg
(0.8ml) sublingually, repeated in 30 mins, if necessary,
and followed by 2mg every 4-6 hours. It may also be
administered subcutaneously (Rivotril injection), giving
2mg SC statim, repeating the dose in half an hour if
necessary, then 8mg per day given by continuous SC
infusion via syringe driver, or as intermittent injections
of 2mg every 6 hours. Clonazepam is miscible with
morphine, hyoscine, haloperidol or metoclopramide
in a syringe driver. It has a long half-life of 22 hours
which may lead to accumulation — this may be an
advantage in this setting. Although up to 70% of the
dose may be unavailable due to adherence to the
plastic of the syringe we have found the above doses
usually effective on the rare occasion that we have
administered as a continuous SC infusion..
• Combining midazolam and clonazepam. In our
experience we have found that some patients who
didn’t respond to high doses of midazolam or
clonazepam were well sedated when switched from
one to the other. It is my approach to order midazolam
30mg S/C infusion over 24 hours with a back-up of
clonazepam 2mg sublingually every 6 hours PRN.
• Rectal diazepam: Statim dose 10–20mg via small
tube (e.g. ‘butterfly’ with needle removed, ‘drawing
up’ tubes or paediatric nasogastric tube), repeated if
necessary in 30–60 minutes, and followed by 20mg
every 8 hours. Although this is an option it is rarely
used these days with the availability of the other
drugs. SC or IM administration of diazepam are not
Symptom Control in Palliative Care - 5th Edition (2013)
recommended because of poor absorption and local
toxicity.
Second-line Treatment Options
• Phenobarbitone sodium. In our experience, when
patients are not adequately sedated by 8mg of
clonazepam plus 30mg midazolam per day, then
increasing these doses is unreliable and patients may
or may not respond. Valuable time can be lost trying
to get an effect. Since we introduced phenobarbitone
sodium to our service we have virtually eliminated the
restless deaths we used to see. The recommended
dose is 400mg subcutaneously every four hours (it may
occasionally need to be given hourly to begin with as
there can be a delay in the drug concentrating in the
brain, and an occasional patient requires 400mg every
2 hours for maintenance). It can be administered in a
separate syringe-driver giving 400mg SC stat, then
2G over 24-hours as a continuous SC infusion. These
doses are higher than usually recommended in the
literature. We believe that these patients are relatively
resistant to sedation and have found lower doses to
be as unreliable as increasing the benzodiazepines. It
is our practice to continue the benzodiazepine when
we commence phenobarbitone. Patients will generally
become settled and calm for the last 24-48 hours of
life much like we would expect if they had settled well
with benzodiazepines.
• Levomepromazine 12.5-25mg S/C statim, then 50200mg S/C via a syringe-driver over 24 hours. The
stat dose may need repeating hourly until settled with
rapid dose escalation to 200mg/24hrs. While this drug
is effective in most cases combined with midazolam
or clonazepam as above we have experienced
several instances of inadequate sedation that didn’t
respond to dose increasing above 200mg/24hours.
All these patients were well sedated when changed to
phenobarbitone. Levomepromazine is available for use
in Australia through the special access scheme (SAS).
Managing Agitation or
Restlessness without Maintaining
Hypnosis until Death
Such an intermediate approach may be desirable in the
following instances:
• Where meaningful communication is still taking place
• When it is requested or demanded by the patient or
family
• Where the symptoms are low grade, not overly
distressing to the patient–family unit and, in the
hospital setting, not interfering with the proper care of
other patients
Symptom Control in Palliative Care - 5th Edition (2013)
• Where there is uncertainty as to a reversible aetiology
or prognosis.
Initial treatment by rectal, sublingual or parenteral
administration may be given in the doses (excluding
phenobarbitone which is not indicated) already outlined,
if initial hypnosis is required, followed by maintenance
therapy in one-third to one-half of the recommended
doses. The dose of drugs may then be titrated until the
desired effect is achieved. These approaches might be
used in a patient with reversible causes of delirium, in
the context of rehydrating with subcutaneous fluids (1-2
litres a day is adequate in cachectic patients) and/or
administering antibiotics, treating hypercalcaemia etc.
Recommended Treatment Options
• Clonazepam 0.5–2mg every 12 hours or at night
• Midazolam 2.5-5mg SC statim, then 10-15mg SC
infusion per 24 hours
• Haloperidol 2-5mg SC statim, then 2-10mg SC per
24 hours as intermittent injections or by continuous
infusion. Haloperidol is recommended in all patients
who are confused and hallucinating in this setting,
usually in combination with a benzodiazepine.
• Diazepam 5–10mg every 12 hours or at night
• Chlorpromazine 25–100mg every 8–12 hours
• Tip: We have found 10-15mg midazolam plus 2-5mg
haloperidol in a syringe driver over 24 hours to be
effective in many patients.
Twitching
Assessment
The aetiology is usually organic and associated with
central irritation. The following causes should be
considered:
• Opiate overdosage. Check for miosis, oversedation,
excess sweating. Reduce the opiate dose and review
current analgesic approaches if pain is still a problem
• Metabolic problems such as hypercalcaemia, hypoxia,
renal failure, liver failure. Myoclonic jerks may be
exacerbated by opiates in this situation. Consider
whether it is appropriate to reverse underlying
problem or change to another opiate, avoiding
morphine in renal failure if possible.
• Drug interactions. This includes use of opiates with
tricyclic antidepressants or major tranquillisers. Drug
management should be reviewed to remove potential
interactions that may cause myoclonic jerks. Drugs with
anticholinergic effects are most likely to be implicated.
There have also been specific reports of this side effect
when gabapentin is used with oxycodone in occasional
patients.
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Treatment in the Non-terminal Phase
• Clonazepam 0.25–1mg at night or every 12 hours
• Diazepam 5–10mg at night or every 12 hours.
• Phenobarbitone elixir 30-60 mg every 8-12 hours and
titrated upwards for effect. This has the potential to
increase the metabolism of other drugs.
• Other anticonvulsants.
Treatment in the Terminal Phase
• Clonazepam as outlined on page 24 if full sedation is
desirable.
• Midazolam as outlined on page 24 if full sedation is
desirable.
• Diazepam as outlined on page 24
• Sodium phenobarbitone starting in a dose outlined
on page 25 if full sedation is desired, or try 50100mg S/C every 8 hours and titrate upwards to
effect. Barbiturates have been reported as successful
in patients where the use of benzodiazepines was
ineffective
• Other anticonvulsants.
Fitting
In patients where death is not imminent, initial treatment
with clonazepam or midazolam (see page 25), or either
rectal or intravenous valium (10mg rectally, 5mg IV) can
be followed by appropriate investigation and ongoing
anticonvulsant management. In patients who are dying,
treatment options include:
• Clonazepam as outlined on page 24
• Midazolam as outlined on page 24
• Sodium phenobarbitone as outlined on page 25 where
full sedation is desirable. Alternatively give 100-200mg
IM stat and repeat in half an hour if convulsions are still
occurring. Maintain with 300-600mg daily by continual
S/C infusion.
Page 26 - click to return to contents
Symptom Control in Palliative Care - 5th Edition (2013)
Alternative Routes for Drug
Administration
Circumstances Requiring Change
from Oral Administration
Commonly Employed Therapeutic
Options
Oral medications are preferred to parenteral or rectal
administration of drugs in palliative care. Common
circumstances requiring change to alternative routes
include the following:
Continuing Effective Pain Control
• Inability to swallow oral medications
• Inability to tolerate oral medications (e.g. nausea and
vomiting)
• Decreased level of consciousness (due to disease
progression or sedation with drugs)
• Inability to absorb oral medications
• Last 24-48 hours of life: Most patients cannot continue
oral medications in this period. Home care in particular
requires familiarity with changing to alternative routes
of administration while maintaining the existing
therapeutic effects of the oral drug regimen.
Principles of Changing from Oral
Drug Administration
• Regular oral medications will have been combined
and instituted for effective control and prevention of
multiple symptoms in palliative care.
• The same control of symptoms must be continued
when changing to alternative routes of administration.
Pain relief must be maintained even in unconscious
patients who might otherwise become agitated
and distressed. This may require strict adherence
to the appropriate combination of an opiate, an
NSAID and other co-analgesics (such as steroids and
anticonvulsants) where these previously formed part of
the oral regime.
• Nausea and vomiting control can be maintained by
parenteral or rectal drug administration.
• Intermittent (4-hourly) or continuous SC administration
of drugs via a syringe driver forms the mainstay of
management.
• Opioid analgesia: Oral morphine, hydromorphone or
oxycodone may be given in one-half the total daily oral
dose divided into intermittent SC injections (4-hourly),
or by a continuous 24-hourly SC infusion via a syringe
driver (using an in situ SC butterfly). Oxycodone
is available parenterally but is expensive and only
available in 10 and 20mg ampoules so it is usual to
switch to morphine or hydromorphone.
• Transdermal fentanyl or Norspan patches are generally
continued with the addition of SC morphine or
hydromorphone. It is common practice to maintain
a fentanyl patch and to add a SC morphine infusion
to titrate the analgesic requirements. Be aware of
the morphine equivalence of the patient’s patch (see
page 11) and commence an infusion (or intermittent
4-hourly injections) that represents approximately a
one-half to one third increase. Parenteral morphine
may be more accessible than the other opioid drugs
but hydromorphone is preferred in renal failure
EGFR<50mls/min.
• Peripherally-effective analgesia should generally be
available, although it is possible that some patients
can manage without these. Our usual practice is to
substitute regular paracetamol or anti-inflammatories
with ketorolac (Toradol) 10-30mg SC every 8-12 hours
in patients with complex pain, or the same dose PRN
in pateints we feel could manage without. Ketorolac
doesn’t combine well with drugs in a syringe-driver
so we give it intermittently via a ‘butterfly’. It can be
used with morphine sulphate alone in a syringe driver.
Administration once daily is often sufficient in a very
terminal phase.
• Paracetamol, and indomethacin (Indocid) can be
administered as suppositories. Administering
paracetamol suppositories every 6 hours is often
impractical, therefore, indomethacin suppositories
100mg every 12-24 hours is recommended.
• If patients have been taking steroids orally, this may be
continued SC with dexamethasone 4–8mg daily. This
must be given at a separate site from other drugs (i.e.
using a second butterfly) as it is incompatible with a
Symptom Control in Palliative Care - 5th Edition (2013)
click to return to contents - Page 27
range of other drugs (except morphine sulphate alone),
forming a precipitate in the syringe driver.
• In patients taking oral tricyclic antidepressants,
amitriptyline can be continued rectally. Although this is
not particularly recommended here it might be useful
in some patients with complex pain.
• In patients taking oral anticonvulsants, sodium
valproate can be continued rectally, clonazepam
drops sublingually, while clonazepam, midazolam and
phenobarbitone sodium may be given by SC route.
It is reasonable to stop current anticonvulsants and
substitute midazolam or clonazepam in the dying
patient.
Continuing Effective Control of Emesis
• Oral haloperidol or metoclopramide can be continued
in the same dosage and interval by intermittent
SC injections or by continual SC infusion over 24
hours via a syringe driver. Either medication may be
administered with morphine in the same syringe
• Drugs recommended for rectal administration may
be inserted into the stoma for therapeutic effect –
assuming they are not returned into the bag.
Combining Drugs in the Syringe Driver
Morphine (or hydromorphone; or methadone), hyoscine,
haloperidol, metoclopramide, promethazine and
midazolam or clonazepam may be combined together
without compatibility problems. Crystalisation may occur
when a high dose of morphine tartrate (the 120mgampule form of morphine) is used in combination with
other drugs.
• Compatibility problems are common with
dexamethasone, phenobarbitone sodium, cyclizine and
ketorolac, which are generally prescribed for separate
SC administration.
• Oral prochlorperazine may be continued by rectal
route in suppository form, although it is usually better
to substitute parenteral alternatives that can be given
by intermittent SC injections or loaded in a syringedriver.
• Promethazine (Phenergan) 25mg SC stat, then 25–
50mg by continuous 24-hour SC infusion, or hyoscine
hydrobromide 0.2-0.4mg SC every 4–8 hours or by
continuous SC infusion may be tried in resistant cases.
• Other parenteral options: 1. Cyclizine 25-50mg SC
stat, then 100-150mg/24hrs by continual SC infusion
via a syringe-driver (cyclizine is incompatible with
many drugs and generally needs to be given in a
separate syringe-driver); 2. Ondansetron (Zofran
injection, 4mg/2ml or 8mg/4ml) 4-8mg SC every 12
hours. Limited compatibility data are available for
ondansetron with other drugs in a syringe-driver but it
can be used with morphine sulphate, midazolam and
metoclopramide; 3. Levomepromazine 6-12.5mg SC
stat, then 12.5-50mg/24hrs by continual SC infusion
mixing well with most other syringe-driver drugs.
Continuing Sedation
• The sedative drugs midazolam or clonazepam
can usually be combined with those required for
controlling pain or emesis in a syringe driver when
this is employed for continual infusion. Clonazepam is
preferably administered as sublingual drops.
• See also pages 24-25 that outline recommended doses
and philosophy.
Patients with Ileostomy or Colostomy
• Rectal route may still be available as above
Page 28 - click to return to contents
Symptom Control in Palliative Care - 5th Edition (2013)
Itching, Ulcers, Bleeding and
Topical Applications
Itch
experience, I have found it possible to stop treatment
after a week without pruritis returning.
This potentially distressing symptom has multiple
etiologies, including:
• Testosterone (Andriol testocaps): 40mg every 12-24
hours.
Dry skin
• Rifampicin (Rimycin, Rifadin): 75mg once daily to
150mg every 12 hours.
• Dry skin is the commonest cause of pruritis in patients
with advanced cancer. Itch should also be treated
when present in patients with pruritis of other origins.
• Locally applied emollients, antipruritic and protective
agents are the mainstay of successful management.
There is a wide range of options available including
(refer to MIMS/Index/Skin):
• Alpha-Keri bath oil – add 20mls to bath tub daily
• Alpha-Keri lotion – apply 3-4 times a day, and as
often as required
• Calamine oily lotion – apply 4 times a day, and as
required (calamine creams and ointments will dry the
skin further)
• Paraffin preparations (eg Cream 45) – apply 3-4
times a day, and as required
• Sorbolene (Sorbolene cream, Hydroderm) – apply
3-4 times a day, and as required
• Try paroxetine (Aropax) 5-20 mg daily in severe and/or
resistant cases.
Histamine-mediated
• Histamine-mediated itch is quite common in the first
week of starting an opioid analgesic medication.
Treatment with an antihistamine for this period is
usually successful.
• It may be associated with allergy, contact dermatitis
or eczema where the mainstay approaches include the
use of anti-histamines, and systemic and local steroid
applications.
• Try paroxetine 5-20mg in resistant cases
Bile salt retention (usually in a jaundiced patient)
• Cholestyramine: is generally not recommended as it
is unpalatable, can cause diarrhoea and often fails to
control pruritis.
Renal failure
• Note that gabapentin and pregabalin have been more
recently adopted as effective drugs for this indication
• Emollient creams/lotions as above, with or without
night sedation
• Gabapentin: 100mg nocte increasing to 100mg every
8 hours if well tolerated. Further increase according to
tolerance and response. Doses above 300mg every 8
hours are not recommended here. For EGFR<15mls/
min use a lower dose commencing 100mg nocte daily
or on alternate days, increasing to bd if necessary and
titrating against response and tolerance to a maximum
dose of 300mg daily. For haemodialysis patients give
100-200mg post-dialysis three days a week.
• Pregabalin: 75mg-150mg every 12 hours. EGFR
30-60mls/min commence on 75mg nocte with
more gradual dose escalation; EGFR 15-29mls/min
commence 25-50mg and titrate up slowly; EGFR
<15mls/min commence 25mg daily; give an extra 25mg
post-haemodialysis in patients on dialysis.
• Mirtazepine 7.5-15mg at bedtime
• Paroxetine 5-10mg orally daily
• Ondansetron: 4-8mg orally or SC every 12 hours
(especially if nausea is present)
Scabies
• Eurax cream or lotion
• Lyclear cream
• Additional note: Paroxetine has particularly
developed in this role and can be trailed in a dose
of 5-20mg daily in most situations where itch is a
persistent symptom.
• Paroxetine (Aropax): 5-20mg orally daily
Malignant and infected ulcers
• Ondansetron (Zofran): 4-8mg orally or SC daily.
This is an expensive option for out-patients as it
is not covered on the PBS scheme. In the author’s
It is not in the scope of this booklet to cover decubitus
ulcers or specific approaches to dressings and
debridement. The main point I wish to put across is the
Symptom Control in Palliative Care - 5th Edition (2013)
click to return to contents - Page 29
importance of managing and preventing odours when
ulcers have a necrotic base and are infected by anaerobic
bacteria.
• Metronidazole (Metronidazole gel, Rosex gel)
dressings: Apply twice daily or with each dressing.
This can be very expensive and an alternative option
is to make up a gel by prescribing metronidazole
suspension (Flagyl S 200mg/5ml) and mixing 2.5mls
(100mg) of this with approximately 10G of IntraSite
gel or hydrogel (Solosite – the cheaper option) and
applying to the wound surface. This could also be
combined with morphine (10mg/10g gel) for local
pain relief and/or sucralfate (Carafate, Ulcyte), 1G
tablet crushed and mixed in the gel for haemostasis.
Care should be taken by the nurse not to have topical
contact with metronidazole preparations. IntraSite and
SoloSite gel preparations are also expensive. Although
most reports of using topical morphine use these gels,
there is probably no reason why other cheaper watersoluble gels (L-gel, KY gel) can’t be utilized if cost
is a problem. Metronidazole tablets can be crushed
and sprinkled, or a suspension of metronidazole for
injection can be sprayed on the wound surface using
an atomizer prior to dressings without mixing in a gel.
Note that complete sterility is not a primary concern
where we are aiming to palliate symptoms rather than
heal wounds.
some instances of vaginal bleeding, using a gel and
applicator.
• Systemic tranexamic acid: 1g every 6-8hours orally,
reducing to 500mg every 8 hours.
• Topical adrenaline: 1:10,000 adrenaline-soaked
non-adherent gauze dressings applied to wound
surface. For large areas it would be wise to dilute the
adrenaline 2-3 fold. There are no guidelines for this
and systemic absorption is possible.
• Antibiotics: Oral or rectal metronidazole can be
given in addition, or as an alternative to local wound
applications. To clean up an infected ulcer combination
with a suitable broad-spectrum antibiotic can be
successful. This is best guided by a wound swab and
culture for sensitivities, and a long-term plan that might
include continuing low-dose antibiotics or antibiotic
rotations. Serious infections complicated by large areas
of ulceration or systemic symptoms are best managed
by initial intra-venous antibiotics if this is considered
appropriate.
Painful Ulcers
• Morphine gel applications as outlined in the
metronidazole section above.
Haemorrhagic Areas
In addition to the use of commercial non-adherent
haemostatic dressings:
• Topical sucralfate: 1g crushed and mixed in 10g of gel
as outlined above in the metronidazole section. Apply
3 times a day.
• Topical tranexamic acid (Cyklokapron): 500mg tablet
crushed and mixed in KY-gel, applied locally 3 times
a day. This has even been reported as effective in
Page 30 - click to return to contents
Symptom Control in Palliative Care - 5th Edition (2013)
The last days of life
Assessment
It is important to recognize when someone is dying to
ensure that every comfort is provided for the patient and
relatives. This includes the withdrawal of unnecessary
medications, the assessment and provision of specific
medications for symptom control, and medical
communication with the patient (if possible) and relatives
about what is happening.
Palliative treatment should be offered as a positive and
active intervention rather than giving the impression
that we are doing nothing for the patient. With skill and
kindness this engages relatives and caregivers in the
process, and doesn’t leave them anxious that they should
have more investigations and treatment. Likewise, they
should not be left with the feeling that they have ‘chosen’
to let their loved-one die, which may happen if you ask
them if they want medications to be withdrawn or to have
sedative drugs started.
It is better to inform them, to listen and to guide them
along the kindest path, imparting the feeling that this
is the best medicine. This is particularly pertinent to
settings where elderly patients deteriorate with multiple
co-morbidities in acute hospitals and nursing homes.
It is an opportunity to create good memories for the
caregivers of a compassionate process and peaceful
death, which has a huge impact on supporting their
bereavement.
Management
• Stop all unnecessary oral medications
• Assess all current symptoms, some of which will be
reported by nurses or care assistants, such as pain or
calling out when moved or turned
• If the patient is having difficulty swallowing change to
parenteral (subcutaneous) and rectal medications (see
page 27 for guidelines on how to change currently
prescribed pain and symptom control medications
from the oral to SC route of administration).
• Knowledge of six drugs is sufficient to manage nearly
all dying (and especially elderly) patients comfortably.
Morphine (alternatively use hydromorphone in 1/5th
the morphine dose) and ketorolac for pain, haloperidol
for nausea and delirium, midazolam or clonazepam for
sedation and hyoscine for respiratory secretions (it is
also a sedative, an anti-emetic and an anti-spasmodic).
It is very useful to have access to a syringe-driver for
continuous SC infusions.
Symptom Control in Palliative Care - 5th Edition (2013)
• Determine whether the patient is comfortably dying
without the need for any medical support, or whether
there is the need for pain management or control of
other symptoms, and whether there is a need to sedate
to manage restlessness or delirium.
• If the patient appears comfortable ensure there are
PRN orders for:
• Morphine 2.5-5mg SC every 4 hours (or onetwelfth of the daily oral morphine dose or a doseequivalence in relation to other prescribed opioids,
e.g. fentanyl patches [see page 11])
• Haloperidol 2.5-5mg SC every 8 hours
• Midazolam 5mg SC every 2 hours, or clonazepam
oral liquid 0.25-1mg sublingual every 6 hours
• Hyoscine hydrobromide 0.4mg SC every 4 hours,
or hyoscine butylbromide 20mg SC every 8 hours.
Initiate either drug and then given regularly at the
first sign of respiratory secretion retention (noisy
breathing).
• If the patient is uncomfortable, in pain, agitated or
affected by other specific symptoms refer to the
appropriate sections of this book. In general the
following combination works well subcutaneously via
a syringe-driver over 24 hours backed up by the PRN
orders above (ie if you’re not sure what to do try this!):
• Morphine 2.5-5mg SC statim, then 10-30mg over
24 hours, beginning with 10mg in an opiate-naive
patient (see morphine conversions on page 11 for
appropriate doses in patients already on opioids).
• Midazolam 2.5-5mg SC statim, then 15-30mg over
24 hours, beginning with 15mg unless the patient is
extremely agitated. In a very agitated patient give
midazolam 5mg SC repeated at half-hourly intervals
until settled (check that urinary retention or rectal
faecal impaction isn’t the cause of the agitation first!)
while starting the infusion
• Clonazepam oral liquid (when midazolam is
not available for the syringe-driver) 0.25-2mg
sublingually every 6 hours, beginning with 0.25mg
unless the patient is extremely agitated in which
case I would commence the regular 2mg dose from
the start (and not less than 1mg).
• Haloperidol 2-5mg SC statim, then 2-5 mg over 24
hours
• Add hyoscine hydrobromide 0.4mg SC statim, then
2.4mg over 24 hours OR hyoscine butylbromide
20mg SC statim, then 40-60mg over 24 hours at
click to return to contents - Page 31
the first sign of noisy respiratory secretions. Use
the hydrobromide preparation if more sedation is
desirable.
• Add ketorolac 10-30mg SC every 12 hours if the
patient still appears to be in pain. Use this from
the beginning if there is a lot of musculo-skeletal
pain, especially in a cachectic patient. Alternatively
prescribe an indomethacin suppository 100mg every
12-24 hours.
• If no syringe-driver is available:
• Give one-sixth of the total oral daily morphine dose
every 4 hours SC (note that this is the same as the
oral dose, which is twice as potent parenterally, so
give a lower dose of 1/12th to 1/6th if pain is not an
issue), or start a fentanyl 12 or 25mcg/hour patch.
If you elect to use the patch remember that you will
have to give morphine (or its equivalent) regularly
4-hourly for the first twelve hours while the patch
‘kicks in’. Then keep the morphine order PRN.
• Use the clonazepam option as above
• Give 2mg haloperidol SC every 12 hours
• Use SC ketorolac or indomethacin suppositories as
above.
• Give hyoscine hydrobromide 0.4mg SC every 4 hours
OR hyoscine butylbromide 20mg SC every 8 hours.
• Please contact your local palliative care service if you
are still having difficulties in achieving patient comfort.
Page 32 - click to return to contents
Symptom Control in Palliative Care - 5th Edition (2013)
Appendix: Renal Failure Doses
Acknowledgement
We are grateful to the renal palliative care service at St
George Hospital for their permission to reproduce the
following table.
Symptom Control in Palliative Care - 5th Edition (2013)
click to return to contents - Page 33
Adaptation of Palliative Care drugs in renal failure by Yorkshire Palliative Medicine Guidelines Group (2006)
and Broadbent et al (2003). For St George End of Life Renal Care Plan
Waiver: All efforts have been made to ensure the accuracy of these guidelines. The best information available has been used. Readers should
exercise clinical judgement in the use of all medications. The authors of this guideline do not accept responsibility for its use in practice.
DRUG
Action in end of
life care
Dose/interval
change in renal
replacement Rx
Amitriptyline (Endep)
Neuropathic Pain Metabolised in the D < 5% excreted
liver.
unchanged in urine
No change to normal
doses.
Buprenorphine
(Norspan) patches
Pain management Norbuprenorphine Renal
(weakly A)
M - 33% in urine
D - 1% unchanged
Faecal
D - 66% unchanged
10-50 ml/min No change Starting dose - 5mg patch changed
<10 ml/min Patches 5mg every 7 days
minimum dose changed
every 7 days
Injection & S/L: Reduce
dose by 2550%. Avoid large single
doses
Dialysed –
Dialysed –
dose as for GFR< dose as for
10mls/min
GFR<
10mls/min
Dialysed –
No
dose as for GFR<
10mls/min
Normal dose
Not dialysed
Not dialysed
METABOLITES
(A=active,
I=inactive)
ELIMINATION
(D=drug,
M=metabolites)
Buscopan (see Hyoscine Butylbromide)
Ceftriaxone
Lower respiratory
infection
Cimetidine
(Magicul. Formerly
manufactured as
Tagamet)
Pruritus
2
(Histamine H
receptor
antagonist)
Clonazepam (Rivotril) Benzodiazepine
Codeine
Weak Opiate
Cyclizine
Antiemetic
(centrally acting)
Breathlessness
Appetite
Dexamethasone
Fentanyl (Durogesic)
patch
Opioid
Inactive
metabolites
Norfentalyl (I)
Page 34 - click to return to contents
Adult Dose with Renal Failure
Starting dose 10mg nocte. Increase
dose according to response and
tolerability.
1g daily IVI
Note: Non-steriodals not recommended in renal failure
PD
Not dialysed
HF
Unknown
No data
HD
Not dialysed
NEPHRO
TOXIC?
(Y/N)
OTHER COMMENTS
No
Contraindicated in Glaucoma, recent AMIs.
Has multiple drug interactions (see MIMS; The Renal Drug
Handbook.)
Side effects - Antihistamine effect - sedation; Anticholinergic
effect - dry mouth, blurred vision, constipation, urinary
retention.
Can cause urinary retention and oedema (non - renal)
CAV/VVHD – not dialysed – dose as GFR 10-20ml/min
"There is a lack of evidence about longer term use in ESRD"
Brown E et al 2007, p. 99
"…it may be a potentially useful analgesic for use in patients
with CKD, although until there are onger term studies the
authors remain cautious about recommending it" Davison EJ et
al (eds) Supportive Care for the Renal Patient 2010, 2nd ed,
OUP.
Dosage should be
Commence 100mg bd; maximum dose 200mg bd
reduced according to
creatinine clearance
(MIMS)
0-15 ml/min 200mg BD
(Chambers et al
recommend 100-200mg
BD)
15-30 ml/min 200mg TDS
30-50 ml/min 200mg QID
>50 ml/min normal dose
Insignificant
Unknown
dialysability. No
change to dosing
regime
No dose adjustment
required
*INCREASED RISK OF
SEDATION IN RENAL
FAILURE
Dose as normal
renal function
Unknown
dialysability
Dose as normal Dose as normal
renal function
renal function
Not dialysed
No
Caution in renal failure.Midazolam infusion may be preferable.
20-50 - normal dose
Maximum Panadeine Forte dose (each
10-20 - 75% normal dose contain 30mg codeine) is 4 / day. See
<10 - 50% dose
commentary in 'Other' column.
dose
Unknown so as
<10
dose
dose
Unknown so as Unknown so as
<10
<10
No
<1% excreted
unchanged in urine
8% unchanged
eliminated in urine
Renal (D,M)
No change to normal
doses.
GFR <10ml/min
Normal dose tapered to
minimum effective dose
50mg tds po/sci/ivi
Unknown
Unknown
Unknown
No
Unknown dialysability
"We advise caution with chronic use of codeine in CKD patients
and suggest limiting doses to 120mg or less per day." Davison
S, Ferro CJ Management of Pain in CKD. Progress in Palliative
Care 2009; 17:186-195.
Dosing according to indication. Typical
commencing dose - 4mg mane. If using
more than one daily dose use mane and
midi dosings only.
Not dialysed
Not dialysed
Unlikely removal
Normal dose
No
D – 9% faecal
D,M - 75% renal
20-50 - normal dose
Minimal commencing dose - 12mcg/hour
10-20 - 75% normal dose patch changed every 3 days.
<10 - 50% dose
1/2 life in ESRD 5
hours
7-aminoRenal (D) <1%
clonazepam (I)
unchanged
7-acetylaminoclonazepam (I)
3-hydroxyclonazepam (A)
C6G (A),
Renal (D,M)
Norcodeine 20-50
10-20 <10
(?),Morphine (A)
M3G (I)M6G (A)
65% (I)
Dose/interval change in
renal failure
GFR
Commence 0.25 - 0.5 mg nocte
Symptom Control in Palliative Care - 5th Edition (2013)
Dose as for GFR Dose as for
<10
GFR <10
Dialysable (1020%)
Recommended
that dosing
occurs post
dialysis
Works as an antihistamine.
2
H receptors in the skin
Be aware of drug interactions (see MIMS)
Accumulation caution in RF
Dose as for GFR No
<10
Symptom Control in Palliative Care - 5th Edition (2013)
Increased cerebral sensitivity in patients with renal failure. Not
recommended in the terminal phase.
"Does not require dose adjustment, but may be complicated by
fluid retension" (Yorkshire Group, 2006. p.9)
For anorexia should consult Renal Dietician. Be aware of the
significant side effects of Dexamethasone in intermediate to
long term use, including and increased susceptibility to
infections, proximal myopathy, impaired glucose tolerance,
hypertension ans osteoporosis.
Not dialysed.
If converting from other opioids to Fentanyl and vice versa
consult opioid conversion charts or the Pain or Palliative Care
teams.
click to return to contents - Page 35
Adaptation of Palliative Care drugs in renal failure by Yorkshire Palliative Medicine Guidelines Group (2006)
and Broadbent et al (2003). For St George End of Life Renal Care Plan
Waiver: All efforts have been made to ensure the accuracy of these guidelines. The best information available has been used. Readers should
exercise clinical judgement in the use of all medications. The authors of this guideline do not accept responsibility for its use in practice.
DRUG
Action in end of
life care
Dose/interval change in
renal failure
GFR
Dose/interval
change in renal
replacement Rx
Gabapentin
(Neurontin)
Neuropathic pain
Uraemic Pruritus
Restless Legs
Syndrome
Adult Dose with Renal Failure
GFR <15ml/min (dialysis) Minimum commencing dose - If on dialysis 100mg
post dialysis. Titrate does by 100mg
Usual maintenance 100increments.
600mg/day or alternate
daily according to effect.
PD
HF
Dose as for GFR Dose as for
<15
GFR <15
HD
Dialysed: Load
300-400mg then
200-300mg after
each HD
No data
Glycopyrrolate
(Robinul)
METABOLITES
(A=active,
I=inactive)
ELIMINATION
(D=drug,
M=metabolites)
Renal (D) eliminated
unchanged in urine
Note: Non-steriodals not recommended in renal failure
If on a conservative non-dialysis pathway (a) If eGFR >50 commence 100mg tds and
titrate up by 100mg increments according to
tolerability and response. See 'Other
Comments' column.
(b) If eGFR 30-49 commence 100mg nocte
– 100mg bd and titrate up by 100mg
increments according to tolerability and
response. See Other Comments column.
(c) If eGFR 15-29 commence 100mg nocte
and titrate up by 100mg increments
according to tolerability and response. See
Other Comments column.
(d) If eGFR < 15 commence 100mg every
second night and titrate up by 100mg
increments according to tolerability and
response. See Other Comments column.
No data
Haloperidol
(Serenace)
Respiratory
secretions
(Terminal)
Agitation,
Hepatic
confusion, nausea metabolism
Hydroxylhaliperidol (A)
Hydromorphone
(Dilaudid)
Opioid
Hyoscine
Butylbromide
(Buscopan)
OTHER COMMENTS
Yes
Dialysis 3x per week lowers the 1/2 life by 60%. Give as
evening dose or post dialysis. May supplement 50% dose post
dialysis if essential
Can cause false positive urinary protein
Interacts with Cimetidine
* Please note that authoritative cautions has been expressed in
the use of Gabapentin in patients with ESRD managed
conservatively: "In the Stage 5 CKD without dialysis it is
preferable not to use" (Murtagh FEM, Weisbord D. Symptom
Management in renal failure. In: Chambers EJ et al (eds).
Supportive Care for the Renal Patient. 2nd ed. 2010. OUP, p.
123.) Please also note the recommendations of the Palliative
Care Formulary (3rd edition, 2008). The authors recommend
the following doses (starting and maximum doses at specific
levels of eGFR) - >80: 300mg tds - 800mg tds; 50-79: 200mg
tds - 400mg tds; 30-49: 300mg daily - 300mg bd; 15-29: 300mg
daily; <15: 300mg alternate days (starting and maximum dose).
After every 4 hours of haemodialysis - supplementary single
dose of 200-300mg.
As a general rule they advise commencing smaller doses
in the elderly. Also in patients with eGFR <15
to "further reduce daily dose in proportion to the
creatinine clearance."
Recommended for terminal secretions in renal
Dose is titrated against effect.
Accumulation possible
D = 48.5% renal
No data
remainder unchanged
in bile
200-400mcg q 2 - 4 hrs sci
No data
Minimal commencing dose - 0.5 mg.
Typical commencing doses for:
* Nausea - 0.5 mg bd
* Delirium - 1mg bd
Not dialysed
No data
Dose as for GFR
<10
Not dialysed
No
Dose as for GFR
<10
Dihydro- <10
isomorphine (A),
dihydromorphine
(A), H3G (I)
Renal(D,M)
Metabolites renally
excreted but inactive
20-50 Normal dose
10-20 Reduce dose
<10 Reduce dose
If opioid naïve typical commencement
dose - 0.5 - 1mg mg q 4hours orally (or
0.25 - 0.5 mg sci)
Titrate according to pain / dyspnea.
Unknown so
dose as for
GFR<10
Unknown so dose No
as
for GFR<10
Unknown
D - 50% renal
excretion
Normal dose
Typical commencement dose 20mg tds qid po/sci. Maximum daily dose 240mg.
Dialysed –
No data
dose as for GFR<
15mls/min
Dialysed –
No
dose as for GFR<
15mls/min
Hyoscine
Hydrobromide
Colicky pain,
terminal
secretions,
malignant bowel
obstruction
Inhibit Excessive
Secretions
Apohyoscine
Dialysable
Normal dose
No data on
dialysability
Normal dose
Dialysable
Normal dose
Ketamine
Neuropathic pain
Nor-ketamine (A)
dehydronorketamine
(I)
30-60 Normal Dose
Not recommended in the Terminal
10-30 Normal dose
Phase with ESRD
<10 or on dialysis, Normal
dose
Not recommended in
ESRD (crosses
blood/brain barrier)
a) Ketamine and
No change
Best be used under the supervision of
norketamine - Renal
the Pain or Palliative Care teams.
5%
Usual practice is to give a test dose of
in urine unchanged +
10mg sci. Monitor for any psychomimetic
5%
effects. After two hours, if tolerated,
unchanged in faeces
commence 100mg sci in a syringe driver
over 24 hours and titrate up by 100mg/
b) Inactive metabolites
day according to efficacy and side effects.
renally excreted
Unlikely to be
dialysed
Not
dialysed dose as for
normal
renal function
Unknown
No
dialysability dose
as for normal
renal
function
NMDA Receptor antagonist.
Can cause urinary retention
and oedema (non - renal)
CAV/VVHD – not dialysed – dose as in GFR
10-20ml/min
20-50% protein bound
Can cause profound psychomimetic effects.
Majority excreted in
urine as M
D- small amount
unchanged in urine
and faeces
Not dialysed No data
dose as for GFR
<10 ml/min
Not dialysed dose as for GFR
<10 ml/min
Started cautiously and at low doses, and titrated according to
response and side effects (Yorkshire Group 2006, p.8)
Can be added after Midazolam for terminal agitation if
symptoms persist (Douglas et al 2009, p.106)
Levomepromazine
(Nozinam)
Restlessness,
a) sulphoxide
metabolite
confusion,
agitation, nausea b) glucuronides
Page 36 - click to return to contents
(M) mainly eliminated
via bile, faeces and
urine
GFR <10ml/min or
dialysis. Begin with low
end of dose range and
titrate according to
response
Excreted in urine,
metabolised in liver
(s/c only 3.4% D
excreted in urine in 72
hrs)
GFR 10-50 - No change
GFR <10 ml/min - start
with small dose
INCREASED RISK OF
SEDATION IN RENAL
FAILURE
Minimal dose - 6.25 mg. Typical
commencement dose - 6.25 mg bd.
Doses are best adjusted according to
symptoms.
Symptom Control in Palliative Care - 5th Edition (2013)
dose as for
normal
renal function
No data
NEPHRO
TOXIC?
(Y/N)
Unknown so
dose as for
GFR<10
No
No
Symptom Control in Palliative Care - 5th Edition (2013)
Elderly should use low doses to avoid extrapyramidal reactions
INCREASED RISK OF SEDATION IN RENAL FAILURE
50% of normal dose recommended (Douglas et al 2009)
Start at low doses in renal failure. "Small risk of accumulating
drug/active metabolite" (Yorkshire Group 2006, p.10)
If converting from other opioids to Hydromorphone and vice
versa consult opioid conversion charts or the Pain or Palliative
Care teams.
Recommended for terminal secretions in renal. No dose
adjustment required.
Anticholinergic - Can cause urinary retention
Not recommended in the terminal phase. Uraemia causes
increased permeability of the blood brain barrier to
centrally acting agents. This may result in Hyoscine
hydrobromide causing paradoxical agitation. (Douglas C,
Murtagh FEM et al. Palliative Medicine 2009;23:103-110).
click to return to contents - Page 37
Adaptation of Palliative Care drugs in renal failure by Yorkshire Palliative Medicine Guidelines Group (2006)
and Broadbent et al (2003). For St George End of Life Renal Care Plan
DRUG
Action in end of
life care
METABOLITES
(A=active,
I=inactive)
Lignocaine
Difficult to manage Active metabolites
Neuropathic pain accumulate during
prolonged
infusions
Lorazepam (Ativan)
Breathlessness,
anxiety
Methadone
Pain
(I) 2-ethylidine-1, 5- (M) in faeces and urine GFR 10-50 Normal dose
Intractable cough dimethyl- , 3GFR <10 50% of normal
diphenylpyrrolidine
dose
, 2-ethyl-3, 3diphenyl-5methylpyrrolidine
(liver)
(I) 70-75% as
glucuronide
metabolites
ELIMINATION
(D=drug,
M=metabolites)
Dose/interval change in
renal failure
GFR
No change
Renal (88%)
Faecal (7%)
GFR <10ml/min or
dialysis. Begin with low
end of dose range and
titrate according to
response
Waiver: All efforts have been made to ensure the accuracy of these guidelines. The best information available has been used. Readers should
exercise clinical judgement in the use of all medications. The authors of this guideline do not accept responsibility for its use in practice.
Note: Non-steriodals not recommended in renal failure
Dose/interval
change in renal
replacement Rx
NEPHRO
TOXIC?
(Y/N)
OTHER COMMENTS
Adult Dose with Renal Failure
Should be used under the supervision of
the Pain or Palliative Care teams.
PD
Unlikely
HF
No data
HD
Not dialysed
No
Caution in prolonged infusion in renal failure-dose modification
if adverse effects
0.5-1mg bd-tds (sublingual or po)
Normal dose
Normal dose
Normal dose
No
CNS adverse effects may be more pronounced in patients with
renal impairment
Should be used under the supervision of
the Pain or Palliative Care teams.
Only recommended to be used by
knowledgeable physicians (Mid-Atlantic
Renal Coalition and the Kidney End-ofLife Coalition. Clinical Algorithms to
Treat Pain in Dialysis Patients. 2009.)
Not dialysed
No data
Dose as for GFR
<10
Not dialysed
No
Dose as for GFR
<10
"Methadone is well cleared in renal failure, but has a very long
half life, even when renal function is normal" (Yorkshire Group
2006, p.10). Use if unable to control pain with Hydromorphine
or Fentanyl (opioid - allergy, adverse events or refractory pain).
(Mid-Atlantic Renal Coalition and the Kidney End-of-Life
Coalition. Clinical Algorithms to Treat Pain in Dialysis Patients .
2009.)
Beware of multiple drug interactions.
There are several recommended dosing
schedules. Given its metabolism - high
oral bioavailability and it accumulates
with repeated dosing - it requires care
and clinical experience to use safely. If
converting from another opioid the
commencement dose is calculated
according to the current background
opioid dose. Accordingly a
commencement dose should be
individualised. For pain, a typical
commencing dose is 2.5mg qid and then
adjusted carefully under the supervision
of the Pain or Palliative Care teams. For
intractable cough commence 5mg - if
cough is mainly nocturnal 5mg nocte; if
cough is day and night 5mg bd.
Metoclopramide
(Maxolon)
Hepatic
Metabolites (I)
Midazolam (Hypnovel) Agitation, End of 1-hydroxymethyl
life crisis sedation midazolam
Morphine
Pain control,
breathlessness
M3G (I) M6G (A)
Octreotide
Malignant bowel
obstruction
(?liver)
Page 38 - click to return to contents
Predominantly renal
(D,M)
GFR 20-50: Normal dose Minimal dose 5 - 10 mg.
GFR 10-20: 75-100% of Typical commencement dose normal dose
5-10mg tds half an hour prior to meals
GFR <10: 50-100% of
normal dose (10mg q812h titrated to response)
Not dialysed
No data
Dose as for GFR
<10
Not dialysed
No
Dose as for GFR
<10
For GFR <20, start at low doses.
Increased risk of extrapyramidal reactions in severe renal
impairment.
Renal (D,M) 45-57%
<1% as unchanged
drug
Renal (D,M)
GFR 10-50 Normal dose
GFR <10 50% of normal
dose
20-50 25% dose
10-20 Small dose
eg start with 2.5-5mg
<10 Small dose eg
start with 1.25 -2.5mg
Typical commencement dose
2.5 mg - 5 mg q 4 hours. Titrate dose
according to symptoms.
Not recommended in Renal Failure.
If no other strong opioid available
commence with small doses
(1-2mg orally tds-qid; 0.5-1mg sci tdsqid) and titrate slowly.
Unlikely
No data
Dose as for GFR
<10
Dose as for GFR Dose as for
<10
GFR <10
Not dialysed
No
Dose as for GFR
<10
Dose as for GFR No
<10
INCREASED RISK OF SEDATION IN RENAL FAILURE. Dose
reduction and an increased dosing interval for midazolam
recommended (Douglas et al 2009, p.106)
Dialysed in HD and CAV (renally excreted, toxic metabolites)
Renal (32%
unchanged)
Normal dose
Commence with 150 mcg tds sci.
Can bring into syringe driver over 24
hours. Maximum dose 1500 mcg over
24 hours
Normal dose
Symptom Control in Palliative Care - 5th Edition (2013)
Likely dialysed, Normal dose
No
no published
Dialysed: plasma
data exists
clearance
increased by
around 30%.
Supplemental
dosing may be
required
Symptom Control in Palliative Care - 5th Edition (2013)
Haemodialysed, unknown peritoneal dialysability
Elimination t1/2 sc=100minutes
click to return to contents - Page 39
Adaptation of Palliative Care drugs in renal failure by Yorkshire Palliative Medicine Guidelines Group (2006)
and Broadbent et al (2003). For St George End of Life Renal Care Plan
Waiver: All efforts have been made to ensure the accuracy of these guidelines. The best information available has been used. Readers should
exercise clinical judgement in the use of all medications. The authors of this guideline do not accept responsibility for its use in practice.
DRUG
Dose/interval
change in renal
replacement Rx
Action in end of
life care
METABOLITES
(A=active,
I=inactive)
ELIMINATION
(D=drug,
M=metabolites)
Dose/interval change in
renal failure
GFR
Ondansetron (Zofran) Pruritus
Nausea
Multiple
metabolites (I)
Renal
<5% unchanged in
urine
Hepatic
Normal dose
Oxycodone
(Endone, Oxycontin,
Oxynorm)
Noroxycodone (A) Renal (D 19%,M 65%) 10-50 Normal
Oxymorphone (A) Faecal (D,M)
dose
<10 Avoid *BEWARE
INCREASED RISK OF
SEDATION IN RENAL
FAILURE
Pain - strong
Opioid
Adult Dose with Renal Failure
Commence 4mg prn.
Regular dose 4-8 mg bd
Endone - minimal dose 2.5mg.
Typical commencement doses - 2.5 mg
tds-qid.
Oxycontin - minimal dose 5mg
Typical commencement dose - 5 mg bd
Note: Non-steriodals not recommended in renal failure
PD
Unlikely
dialysability.
Dose as for
normal renal
function
Unknown
dialysability
Dose as for GFR
<10
NEPHRO
TOXIC?
(Y/N)
OTHER COMMENTS
No
Can be used to treat uraemic Pruritus.
NOTE: Ondansetron is very constipating
HF
Unknown
Dose as for
normal renal
function
HD
Not dialysed.
Dose as for
normal renal
function.
Unknown
dialysability
Dose as for
GFR <10
Unknown
No
dialysability
Dose as for GFR
<10
Oxycodone: "There are no long term studies of chronic use in
renal failure and the conflicting case reports mean there is
insufficient evidence currently for a recommendation." Davison
S, Chambers EJ & Ferro CJ. Management of pain in renal
failure. In Chambers et al (eds) Supportive Care for the Renal
Patient 2010, 2nd ed, OUP.
*Used in ESRF – low doses of Oxynorm
Metabolites may be more likely to
accumulate and cause sedation, than
hydromorphone metabolites at very low GFRs
GFR<60 increased plasma concentration of
active drug by 20-50%
Paracetamol
Pregabalin (Lyrica)
Simple pain relief Glucuronide,
sulphate 10-50
<10
and glutathione
conjugates (I)
Neuropathic pain Undergoes
Uraemic Pruritus negligible
Restless Legs
metabolism
Syndrome
Renal (D and M, only
3%
unchanged)
10-50 Normal dose
<10 500mg- 1g 6-8hrs
Typical dose 1g
If on dialysis – commence 25 mg daily and
Renally excreted as an Dosing schedule with
unchanged drug
normal renal function is a titrate according to tolerability and response.
(The
Renal Drug Handbook, 3rd ed). MIMS
bd dose.
Dose as GFR<10
Dose as GFR<10 Yes in
overdose
Not removed by PD
Known to be removed by HD
Normal doses are very often used in ESRD
Dialysed
Dialysed
50% removal
after 4 hours of
HD
No
Is a Gabapentanoid medication.
Use with caution in patients with severe Congestive Cardiac
Failure (The Renal Drug Handbook, 3rd ed)
Unknown
dialysability
Normal dose
Unknown
dialysability
Normal dose
Not dialysed
Normal dose
No
Alter doses according to FREE serum levels
INCREASED RISK OF SEDATION IN RENAL FAILURE
Unknown
dialysability
Data sheet
advises against
use
Unknown
dialysability
Data sheet
advises against
use
Slowly dialysed
Data sheet
advises against
use
No
Although data sheet advises against use in
PD, HD & GFR <10, Renal Drug Handbook
suggests using doses of 50mg 12 hourly.
Avoid using with SSRIs
Unknown
dialysability
Dose as for GFR
<10
Unknown
dialysability
Dose as for
GFR <10
Unknown
No
dialysability
Dose as for GFR
<10
recommends giving an extra 25mg after
each dialysis.
With CKD need to reduce
If on a conservative pathway –
to a daily dose.
(a) If eGFR 30-60 – commence 75 mg daily
and titrate according to tolerability and response.
(b) If eGFR 15-29 – commence 25-50mg daily
and titrate according to tolerability and response.
(c) If eGFR <15 – commence 25mg daily
and titrate according to tolerability and
response. (The Renal Drug Handbook, 3rd ed)
Sodium Valproate
(Epilim)
Neuropathic pain
Tramadol (Tramal)
Tranexamic acid
Clot stabiliser for
bleeding
None
Liver (D)
5% excreted
unchanged in urine
O-desmethyltramadol
(A)
N-desmethyltramadol
(A)
Renal (D,M) 90%
Faecal(D) 10%
None
Renal (D)
90% by glomerular
filtration in 24hrs (IV
dose). 39% at 24hr &
41% at 48hr (oral
dose), <5% as M in
urine
GFR <10ml/min Normal Commence - 200mg bd
dose tapered to minimum
effective dose (and blood
conc)
20-50 Normal dose
10-20 50 -100mg
12hourly
<10 Data sheet
advises against use
If on dialysis commence 50mg bd;
maximum 100bd.
GFR 10-30 1000-1500mg
od.
GFR <10ml/min 5001000mg od after dialysis
eGFR 30 - 60 - commence 1 - 1.5g bdtds
eGFR 10-30 - commence 1 - 1.5g daily
eGFR <10 - commence 500mg - 1g
daily
If on a conservative pathway :
(a) If eGFR >30 – dose as in normal
renal function.
(b) If eGFR 15-30 – commence 50mg
bd; maximum 100mg bd
(c) If eGFR <15 – 50mg bd (maximum).
Bibliography
Ashley, C. Currie, A (eds). 2009. The Renal Drug Handbook, 3rd edition. Radcliffe Publishing UK
Broadbent, A. Khor, K. Heaney, A. 2003. Palliation and Chronic Renal Failure: Opioid and Other Palliative Medications - Dosage Guidelines. 2003. Progress in Palliative Care 11(4), pp 183-190
Brown E et al (eds) End of Life Care in Nephrology. 2007, p.99.
Cervelli, M. The Renal Drug Reference Guide, 1st edition, 2007. Nexus Printing, Adelaide
Chambers, J. Brown, E. Germain, M. 2005. Supportive Care for the Renal Patient. Oxford University Press, UK
Chambers, J. Brown, E. Germain, M. eds 2010. Supportive Care for the Renal Patient, 2nd edition. Oxford University Press, UK
Davison S. Chambers, EJ. Ferro, CJ. Management of pain in renal failure. Chambers, J. Brown, E. Germain, M. eds 2010.
Supportive Care for the Renal Patient, 2nd edition. Oxford University Press, UK
Page 40 - click to return to contents
Symptom Control in Palliative Care - 5th Edition (2013)
Unknown dialysability
Dose as for GFR <10
Davison S, Ferro CJ. Management of Pain in CKD. Progress in Palliative Care 2009; 17:186-195.
Department of Health. Renal NSF Team and Marie Curie Palliative Care Institute. National LCP Renal Steering Group. 2008. Guidelines for LCP Prescribing in
Advanced Chronic Kidney Disease. Downloaded 4.5.09 http://www.mcpcil.org.uk/files/NationalLCPRenalsymptomcontrolguidelinesJuneprintablepdf_0.pdf
Douglas, C. Murtagh, F. Chambers, E. Howse, M. & Ellershaw, J. 2009. Symptom management for the adult patient dying with advanced chronic kidney disease:
A review of the literature and development of evidence-based guidelines by a United Kingdom Expert Consensus Group. Palliative Medicine, 23, pp 103-110
Edwards, A, Yorkshire Palliative Medicine Guidelines Group. 2006. Clinical Guidelines for the use of Palliative Care Drugs in Renal Failure.
Johnson, C. 2009, Dialysis of Drugs 2009 , CKD Insights USA and Amgen Australia Pty Ltd.
Mid-Atlantic Renal Coalition (MARC) and the Kidney End-of-Life Coalition. Clinical Algorithms to Treat Pain in Dialysis Patients . 2009
Palliative Care Formulary (3rd edition, 2008)
Symptom Control in Palliative Care - 5th Edition (2013)
click to return to contents - Page 41
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